{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:45:43Z","timestamp":1792788343087,"version":"4.5.0"},"reference-count":126,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Silo Pharma"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Alz Res Therapy"],"DOI":"10.1186\/s13195-025-01804-9","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T09:06:36Z","timestamp":1752570396000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Combinatorial targeting of NMDARs and 5-HT4Rs exerts beneficial effects in a mouse model of Alzheimer\u2019s disease"],"prefix":"10.1186","volume":"17","author":[{"given":"Briana K.","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly C.","family":"Hunsberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Whye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise C.","family":"Matthews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyson","family":"Yook","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moshe J.","family":"Willner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan W.","family":"Logan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Johns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Weisblum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine A.","family":"Denny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"1804_CR1","first-page":"5789","volume":"25","author":"Z Breijyeh","year":"2020","unstructured":"Breijyeh Z, Karaman R. Comprehensive review on Alzheimer\u2019s disease: causes and treatment. Mol Basel Switz. 2020;25:5789.","journal-title":"Mol Basel Switz"},{"key":"1804_CR2","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.2174\/1570159X18666200528142429","volume":"18","author":"S Khan","year":"2020","unstructured":"Khan S, Barve KH, Kumar MS. Recent advancements in pathogenesis, diagnostics and treatment of Alzheimer\u2019s disease. Curr Neuropharmacol. 2020;18:1106\u201325.","journal-title":"Curr Neuropharmacol"},{"key":"1804_CR3","doi-asserted-by":"publisher","first-page":"779","DOI":"10.3233\/JAD-180766","volume":"67","author":"JL Cummings","year":"2019","unstructured":"Cummings JL, Tong G, Ballard C. Treatment combinations for Alzheimer\u2019s disease: current and future pharmacotherapy options. J Alzheimers Dis JAD. 2019;67:779\u201394.","journal-title":"J Alzheimers Dis JAD"},{"key":"1804_CR4","unstructured":"NIA-funded active Alzheimer\u2019s and related dementias clinical trials and studies. Natl Inst Aging. Available from: https:\/\/www.nia.nih.gov\/research\/ongoing-AD-trials. Cited 2025 Feb 13."},{"issue":"24","key":"1804_CR5","first-page":"01621","volume":"S0006\u20133223","author":"HC Hunsberger","year":"2024","unstructured":"Hunsberger HC, Lee S, Jin M, Lanio M, Whye A, Cha J, et al. Sex-specific effects of anxiety on cognition and activity-dependent neural networks: insights from (Female) mice and (Wo)men. Biol Psychiatry. 2024;S0006\u20133223(24):01621\u20134.","journal-title":"Biol Psychiatry"},{"key":"1804_CR6","doi-asserted-by":"publisher","first-page":"18008","DOI":"10.1523\/JNEUROSCI.1402-13.2013","volume":"33","author":"LL Beason-Held","year":"2013","unstructured":"Beason-Held LL, Goh JO, An Y, Kraut MA, O\u2019Brien RJ, Ferrucci L, et al. Changes in brain function occur years before the onset of cognitive impairment. J Neurosci Off J Soc Neurosci. 2013;33:18008\u201314.","journal-title":"J Neurosci Off J Soc Neurosci"},{"key":"1804_CR7","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/j.jagp.2014.10.005","volume":"23","author":"L Mah","year":"2015","unstructured":"Mah L, Binns MA, Steffens DC, Alzheimer\u2019s Disease Neuroimaging Initiative. Anxiety symptoms in amnestic mild cognitive impairment are associated with medial temporal atrophy and predict conversion to Alzheimer disease. Am J Geriatr Psychiatry Off J Am Assoc Geriatr Psychiatry. 2015;23:466\u201376.","journal-title":"Am J Geriatr Psychiatry Off J Am Assoc Geriatr Psychiatry."},{"key":"1804_CR8","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1176\/appi.ajp.2017.17040442","volume":"175","author":"NJ Donovan","year":"2018","unstructured":"Donovan NJ, Locascio JJ, Marshall GA, Gatchel J, Hanseeuw BJ, Rentz DM, et al. Longitudinal association of amyloid beta and anxious-depressive symptoms in cognitively normal older adults. Am J Psychiatry. 2018;175:530\u20137.","journal-title":"Am J Psychiatry"},{"key":"1804_CR9","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1146\/annurev-med-051322-120608","volume":"75","author":"J-W Kim","year":"2024","unstructured":"Kim J-W, Suzuki K, Kavalali ET, Monteggia LM. Ketamine: mechanisms and relevance to treatment of depression. Annu Rev Med. 2024;75:129\u201343.","journal-title":"Annu Rev Med"},{"key":"1804_CR10","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/s41386-023-01629-w","volume":"49","author":"JH Krystal","year":"2024","unstructured":"Krystal JH, Kavalali ET, Monteggia LM. Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2024;49:41\u201350.","journal-title":"Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol"},{"key":"1804_CR11","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/S0006-3223(99)00230-9","volume":"47","author":"RM Berman","year":"2000","unstructured":"Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, et al. Antidepressant effects of ketamine in depressed patients. Biol Psychiatry. 2000;47:351\u20134.","journal-title":"Biol Psychiatry"},{"key":"1804_CR12","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1038\/nm.4050","volume":"22","author":"RS Duman","year":"2016","unstructured":"Duman RS, Aghajanian GK, Sanacora G, Krystal JH. Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants. Nat Med. 2016;22:238\u201349.","journal-title":"Nat Med"},{"key":"1804_CR13","doi-asserted-by":"publisher","first-page":"401","DOI":"10.3233\/JAD-170424","volume":"60","author":"T Kishi","year":"2017","unstructured":"Kishi T, Matsunaga S, Oya K, Nomura I, Ikuta T, Iwata N. Memantine for Alzheimer\u2019s disease: an updated systematic review and meta-analysis. J Alzheimers Dis JAD. 2017;60:401\u201325.","journal-title":"J Alzheimers Dis JAD"},{"key":"1804_CR14","doi-asserted-by":"publisher","first-page":"e0123289","DOI":"10.1371\/journal.pone.0123289","volume":"10","author":"S Matsunaga","year":"2015","unstructured":"Matsunaga S, Kishi T, Iwata N. Memantine monotherapy for Alzheimer\u2019s disease: a systematic review and meta-analysis. PLoS ONE. 2015;10:e0123289.","journal-title":"PLoS ONE"},{"key":"1804_CR15","doi-asserted-by":"publisher","first-page":"310","DOI":"10.3390\/neurolint14020025","volume":"14","author":"IM Shehata","year":"2022","unstructured":"Shehata IM, Masood W, Nemr N, Anderson A, Bhusal K, Edinoff AN, et al. The possible application of ketamine in the treatment of depression in Alzheimer\u2019s disease. Neurol Int. 2022;14:310.","journal-title":"Neurol Int"},{"key":"1804_CR16","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.brainresbull.2016.05.016","volume":"126","author":"Y Liu","year":"2016","unstructured":"Liu Y, Lin D, Wu B, Zhou W. Ketamine abuse potential and use disorder. Brain Res Bull. 2016;126:68\u201373.","journal-title":"Brain Res Bull"},{"key":"1804_CR17","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/S2215-0366(17)30272-9","volume":"5","author":"B Short","year":"2018","unstructured":"Short B, Fong J, Galvez V, Shelker W, Loo CK. Side-effects associated with ketamine use in depression: a systematic review. Lancet Psychiatry. 2018;5:65\u201378.","journal-title":"Lancet Psychiatry"},{"key":"1804_CR18","doi-asserted-by":"publisher","first-page":"112841","DOI":"10.1016\/j.bbr.2020.112841","volume":"394","author":"KA Trujillo","year":"2020","unstructured":"Trujillo KA, I\u00f1iguez SD. Ketamine beyond anesthesia: Antidepressant effects and abuse potential. Behav Brain Res. 2020;394:112841.","journal-title":"Behav Brain Res"},{"key":"1804_CR19","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.expneurol.2007.02.001","volume":"205","author":"F Lezoualc\u2019h","year":"2007","unstructured":"Lezoualc\u2019h F. 5-HT4 receptor and Alzheimer\u2019s disease: the amyloid connection. Exp Neurol. 2007;205:325\u20139.","journal-title":"Exp Neurol"},{"key":"1804_CR20","doi-asserted-by":"publisher","first-page":"781","DOI":"10.4155\/fmc-2017-0031","volume":"9","author":"J Lalut","year":"2017","unstructured":"Lalut J, Karila D, Dallemagne P, Rochais C. Modulating 5-HT4 and 5-HT6 receptors in Alzheimer\u2019s disease treatment. Future Med Chem. 2017;9:781\u201395.","journal-title":"Future Med Chem"},{"key":"1804_CR21","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1111\/j.1476-5381.1996.tb15309.x","volume":"117","author":"J Ge","year":"1996","unstructured":"Ge J, Barnes NM. 5-HT4 receptor-mediated modulation of 5-HT release in the rat hippocampus in vivo. Br J Pharmacol. 1996;117:1475\u201380.","journal-title":"Br J Pharmacol"},{"key":"1804_CR22","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1017\/S1461145711000782","volume":"15","author":"J Pascual-Brazo","year":"2012","unstructured":"Pascual-Brazo J, Castro E, D\u00edaz A, Valdiz\u00e1n EM, Pilar-Cu\u00e9llar F, Vidal R, et al. Modulation of neuroplasticity pathways and antidepressant-like behavioural responses following the short-term (3 and 7 days) administration of the 5-HT\u2084 receptor agonist RS67333. Int J Neuropsychopharmacol. 2012;15:631\u201343.","journal-title":"Int J Neuropsychopharmacol"},{"key":"1804_CR23","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1038\/s41386-019-0540-3","volume":"45","author":"BK Chen","year":"2020","unstructured":"Chen BK, Mendez-David I, Luna VM, Faye C, Gardier AM, David DJ, et al. Prophylactic efficacy of 5-HT4R agonists against stress. Neuropsychopharmacology. 2020;45:542\u201352.","journal-title":"Neuropsychopharmacology"},{"key":"1804_CR24","doi-asserted-by":"crossref","unstructured":"Chen BK, Luna VM, Jin M, Shah A, Shannon ME, Pauers M, et al. A tale of two receptors: simultaneous targeting of NMDARs and 5-HT 4 Rs exerts additive effects against stress. bioRxiv. 2023;2023.09.27.559065.","DOI":"10.1101\/2023.09.27.559065"},{"key":"1804_CR25","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.1038\/npp.2013.332","volume":"39","author":"I Mendez-David","year":"2014","unstructured":"Mendez-David I, David DJ, Darcet F, Wu MV, Kerdine-R\u00f6mer S, Gardier AM, et al. Rapid anxiolytic effects of a 5-HT\u2084 receptor agonist are mediated by a neurogenesis-independent mechanism. Neuropsychopharmacology. 2014;39:1366\u201378.","journal-title":"Neuropsychopharmacology"},{"key":"1804_CR26","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/j.biopsych.2019.08.009","volume":"87","author":"C Faye","year":"2020","unstructured":"Faye C, Hen R, Guiard BP, Denny CA, Gardier AM, Mendez-David I, et al. Rapid anxiolytic effects of RS67333, a serotonin type 4 receptor agonist, and diazepam, a benzodiazepine, are mediated by projections from the prefrontal cortex to the dorsal raphe nucleus. Biol Psychiatry. 2020;87:514\u201325.","journal-title":"Biol Psychiatry"},{"key":"1804_CR27","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.neuropharm.2014.05.013","volume":"85","author":"AC Lo","year":"2014","unstructured":"Lo AC, De Maeyer JH, Vermaercke B, Callaerts-Vegh Z, Schuurkes JAJ, D\u2019Hooge R. SSP-002392, a new 5-HT4 receptor agonist, dose-dependently reverses scopolamine-induced learning and memory impairments in C57Bl\/6 mice. Neuropharmacology. 2014;85:178\u201389.","journal-title":"Neuropharmacology"},{"key":"1804_CR28","doi-asserted-by":"publisher","first-page":"2365","DOI":"10.1007\/s00213-017-4664-z","volume":"234","author":"T Freret","year":"2017","unstructured":"Freret T, Lelong-Boulouard V, Lecouflet P, Hamidouche K, Dauphin F, Boulouard M. Co-modulation of an allosteric modulator of nicotinic receptor-cholinesterase inhibitor (galantamine) and a 5-HT4 receptor agonist (RS-67333): effect on scopolamine-induced memory deficit in the mouse. Psychopharmacology. 2017;234:2365\u201374.","journal-title":"Psychopharmacology"},{"key":"1804_CR29","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1038\/sj.bjp.0707178","volume":"150","author":"M Cachard-Chastel","year":"2007","unstructured":"Cachard-Chastel M, Lezoualc\u2019h F, Dewachter I, Delom\u00e9nie C, Croes S, Devijver H, et al. 5-HT4 receptor agonists increase sAPPalpha levels in the cortex and hippocampus of male C57BL\/6j mice. Br J Pharmacol. 2007;150:883\u201392.","journal-title":"Br J Pharmacol"},{"key":"1804_CR30","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/S0278-5846(02)00351-2","volume":"27","author":"L Lamirault","year":"2003","unstructured":"Lamirault L, Guillou C, Thal C, Simon H. Combined treatment with galanthaminium bromide, a new cholinesterase inhibitor, and RS 67333, a partial agonist of 5-HT4 receptors, enhances place and object recognition in young adult and old rats. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27:185\u201395.","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"1804_CR31","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1017\/S0033291720000604","volume":"51","author":"SE Murphy","year":"2021","unstructured":"Murphy SE, de Cates AN, Gillespie AL, Godlewska BR, Scaife JC, Wright LC, et al. Translating the promise of 5HT4 receptor agonists for the treatment of depression. Psychol Med. 2021;51:1111\u201320.","journal-title":"Psychol Med"},{"key":"1804_CR32","doi-asserted-by":"publisher","first-page":"2722","DOI":"10.1017\/S0033291719002836","volume":"50","author":"SE Murphy","year":"2020","unstructured":"Murphy SE, Wright LC, Browning M, Cowen PJ, Harmer CJ. A role for 5-HT4 receptors in human learning and memory. Psychol Med. 2020;50:2722\u201330.","journal-title":"Psychol Med"},{"key":"1804_CR33","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.neuropharm.2017.08.031","volume":"126","author":"K Baranger","year":"2017","unstructured":"Baranger K, Giannoni P, Girard SD, Girot S, Gaven F, Stephan D, et al. Chronic treatments with a 5-HT4 receptor agonist decrease amyloid pathology in the entorhinal cortex and learning and memory deficits in the 5xFAD mouse model of Alzheimer\u2019s disease. Neuropharmacology. 2017;126:128\u201341.","journal-title":"Neuropharmacology"},{"key":"1804_CR34","doi-asserted-by":"publisher","first-page":"147701","DOI":"10.1016\/j.brainres.2021.147701","volume":"1773","author":"N Hashemi-Firouzi","year":"2021","unstructured":"Hashemi-Firouzi N, Shahidi S, Soleimani AS. Chronic stimulation of the serotonergic 5-HT4 receptor modulates amyloid-beta-related impairments in synaptic plasticity and memory deficits in male rats. Brain Res. 2021;1773:147701.","journal-title":"Brain Res"},{"key":"1804_CR35","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1016\/j.neuropharm.2004.06.033","volume":"47","author":"E Marchetti","year":"2004","unstructured":"Marchetti E, Chaillan FA, Dumuis A, Bockaert J, Soumireu-Mourat B, Roman FS. Modulation of memory processes and cellular excitability in the dentate gyrus of freely moving rats by a 5-HT4 receptors partial agonist, and an antagonist. Neuropharmacology. 2004;47:1021\u201335.","journal-title":"Neuropharmacology"},{"key":"1804_CR36","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1016\/S0028-3908(01)00123-X","volume":"41","author":"L Lamirault","year":"2001","unstructured":"Lamirault L, Simon H. Enhancement of place and object recognition memory in young adult and old rats by RS-67,333, a partial agonist of 5-HT4 receptors. Neuropharmacology. 2001;41:844\u201353.","journal-title":"Neuropharmacology"},{"key":"1804_CR37","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1101\/lm.67303","volume":"10","author":"M Orsetti","year":"2003","unstructured":"Orsetti M, Dellarole A, Ferri S, Ghi P. Acquisition, retention, and recall of memory after injection of RS-67,333, a 5-HT(4) receptor agonist, into the nucleus basalis magnocellularis of the rat. Learn Mem Cold Spring Harb N. 2003;10:420\u20136.","journal-title":"Learn Mem Cold Spring Harb N"},{"key":"1804_CR38","doi-asserted-by":"publisher","first-page":"2017","DOI":"10.1016\/S0028-3908(00)00038-1","volume":"39","author":"E Marchetti","year":"2000","unstructured":"Marchetti E, Dumuis A, Bockaert J, Soumireu-Mourat B, Roman FS. Differential modulation of the 5-HT(4) receptor agonists and antagonist on rat learning and memory. Neuropharmacology. 2000;39:2017\u201327.","journal-title":"Neuropharmacology"},{"key":"1804_CR39","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.nlm.2008.03.010","volume":"90","author":"E Marchetti","year":"2008","unstructured":"Marchetti E, Jacquet M, Jeltsch H, Migliorati M, Nivet E, Cassel JC, et al. Complete recovery of olfactory associative learning by activation of 5-HT4 receptors after dentate granule cell damage in rats. Neurobiol Learn Mem. 2008;90:185\u201391.","journal-title":"Neurobiol Learn Mem"},{"key":"1804_CR40","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/j.bbr.2007.10.008","volume":"187","author":"M Cachard-Chastel","year":"2008","unstructured":"Cachard-Chastel M, Devers S, Sicsic S, Langlois M, Lezoualc\u2019h F, Gardier AM, et al. Prucalopride and donepezil act synergistically to reverse scopolamine-induced memory deficit in C57Bl\/6j mice. Behav Brain Res. 2008;187:455\u201361.","journal-title":"Behav Brain Res"},{"key":"1804_CR41","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/s41398-021-01568-4","volume":"11","author":"AN de Cates","year":"2021","unstructured":"de Cates AN, Wright LC, Martens MAG, Gibson D, T\u00fcrkmen C, Filippini N, et al. D\u00e9j\u00e0-vu? Neural and behavioural effects of the 5-HT4 receptor agonist, prucalopride, in a hippocampal-dependent memory task. Transl Psychiatry. 2021;11:497.","journal-title":"Transl Psychiatry"},{"key":"1804_CR42","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.neuroscience.2004.06.070","volume":"129","author":"JP Spencer","year":"2004","unstructured":"Spencer JP, Brown JT, Richardson JC, Medhurst AD, Sehmi SS, Calver AR, et al. Modulation of hippocampal excitability by 5-HT4 receptor agonists persists in a transgenic model of Alzheimer\u2019s disease. Neuroscience. 2004;129:49\u201354.","journal-title":"Neuroscience"},{"key":"1804_CR43","doi-asserted-by":"publisher","first-page":"1338502","DOI":"10.3389\/fncel.2024.1338502","volume":"18","author":"S Jiang","year":"2024","unstructured":"Jiang S, Sydney EJ, Runyan AM, Serpe R, Srikanth M, Figueroa HY, et al. 5-HT4 receptor agonists treatment reduces tau pathology and behavioral deficit in the PS19 mouse model of tauopathy. Front Cell Neurosci. 2024;18:1338502.","journal-title":"Front Cell Neurosci"},{"key":"1804_CR44","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1016\/j.neurobiolaging.2013.01.020","volume":"34","author":"I Tesseur","year":"2013","unstructured":"Tesseur I, Pimenova AA, Lo AC, Ciesielska M, Lichtenthaler SF, De Maeyer JH, et al. Chronic 5-HT4 receptor activation decreases A\u03b2 production and deposition in hAPP\/PS1 mice. Neurobiol Aging. 2013;34:1779\u201389.","journal-title":"Neurobiol Aging"},{"key":"1804_CR45","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1016\/j.neurobiolaging.2003.09.008","volume":"25","author":"JL Jankowsky","year":"2004","unstructured":"Jankowsky JL, Slunt HH, Gonzales V, Jenkins NA, Copeland NG, Borchelt DR. APP processing and amyloid deposition in mice haplo-insufficient for presenilin 1. Neurobiol Aging. 2004;25:885\u201392.","journal-title":"Neurobiol Aging"},{"key":"1804_CR46","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1002\/hipo.22756","volume":"27","author":"JN Perusini","year":"2017","unstructured":"Perusini JN, Cajigas SA, Cohensedgh O, Lim SC, Pavlova IP, Donaldson ZR, et al. Optogenetic stimulation of dentate gyrus engrams restores memory in Alzheimer\u2019s disease mice. Hippocampus. 2017;27:1110\u201322.","journal-title":"Hippocampus"},{"key":"1804_CR47","doi-asserted-by":"publisher","first-page":"12171","DOI":"10.1038\/s41598-020-68739-z","volume":"10","author":"HC Hunsberger","year":"2020","unstructured":"Hunsberger HC, Greenwood BP, Tolstikov V, Narain NR, Kiebish MA, Denny CA. Divergence in the metabolome between natural aging and Alzheimer\u2019s disease. Sci Rep. 2020;10:12171.","journal-title":"Sci Rep"},{"key":"1804_CR48","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1038\/s41386-020-0714-z","volume":"45","author":"BK Chen","year":"2020","unstructured":"Chen BK, Luna VM, LaGamma CT, Xu X, Deng S-X, Suckow RF, et al. Sex-specific neurobiological actions of prophylactic (R,S)-ketamine, (2R,6R)-hydroxynorketamine, and (2S,6S)-hydroxynorketamine. Neuropsychopharmacology. 2020;45:1545\u201356.","journal-title":"Neuropsychopharmacology"},{"key":"1804_CR49","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1038\/s41386-019-0570-x","volume":"45","author":"JL Phillips","year":"2020","unstructured":"Phillips JL, Norris S, Talbot J, Hatchard T, Ortiz A, Birmingham M, et al. Single and repeated ketamine infusions for reduction of suicidal ideation in treatment-resistant depression. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2020;45:606\u201312.","journal-title":"Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol"},{"key":"1804_CR50","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1176\/appi.ajp.2020.20050596","volume":"178","author":"A Feder","year":"2021","unstructured":"Feder A, Costi S, Rutter SB, Collins AB, Govindarajulu U, Jha MK, et al. A randomized controlled trial of repeated ketamine administration for chronic posttraumatic stress disorder. Am J Psychiatry. 2021;178:193\u2013202.","journal-title":"Am J Psychiatry"},{"key":"1804_CR51","doi-asserted-by":"publisher","first-page":"5968","DOI":"10.3390\/ijms23115968","volume":"23","author":"M Bia\u0142o\u0144","year":"2022","unstructured":"Bia\u0142o\u0144 M, W\u0105sik A. Advantages and limitations of animal schizophrenia models. Int J Mol Sci. 2022;23:5968.","journal-title":"Int J Mol Sci"},{"key":"1804_CR52","doi-asserted-by":"publisher","first-page":"S51","DOI":"10.3233\/JAD-201059","volume":"82","author":"L Guzman-Martinez","year":"2021","unstructured":"Guzman-Martinez L, Calf\u00edo C, Farias GA, Vilches C, Prieto R, Maccioni RB. New frontiers in the prevention, diagnosis, and treatment of Alzheimer\u2019s disease. J Alzheimers Dis JAD. 2021;82:S51-63.","journal-title":"J Alzheimers Dis JAD"},{"key":"1804_CR53","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/978-3-030-05542-4_15","volume":"1118","author":"FL Guest","year":"2019","unstructured":"Guest FL. Early detection and treatment of patients with Alzheimer\u2019s disease: future perspectives. Adv Exp Med Biol. 2019;1118:295\u2013317.","journal-title":"Adv Exp Med Biol"},{"key":"1804_CR54","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1007\/978-3-030-42667-5_8","volume":"1260","author":"FL Guest","year":"2020","unstructured":"Guest FL, Rahmoune H, Guest PC. Early diagnosis and targeted treatment strategy for improved therapeutic outcomes in Alzheimer\u2019s disease. Adv Exp Med Biol. 2020;1260:175\u201391.","journal-title":"Adv Exp Med Biol"},{"key":"1804_CR55","doi-asserted-by":"publisher","first-page":"1309","DOI":"10.3390\/cells12091309","volume":"12","author":"KY Kim","year":"2023","unstructured":"Kim KY, Shin KY, Chang K-A. GFAP as a potential biomarker for Alzheimer\u2019s disease: a systematic review and meta-analysis. Cells. 2023;12:1309.","journal-title":"Cells"},{"key":"1804_CR56","doi-asserted-by":"publisher","first-page":"93","DOI":"10.3390\/biom14010093","volume":"14","author":"G Garcia-Escobar","year":"2024","unstructured":"Garcia-Escobar G, Manero RM, Fern\u00e1ndez-Lebrero A, Ois A, Navalpotro-G\u00f3mez I, Puente-Periz V, et al. Blood Biomarkers of Alzheimer\u2019s disease and cognition: a literature review. Biomolecules. 2024;14:93.","journal-title":"Biomolecules"},{"key":"1804_CR57","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1186\/s13195-022-01051-2","volume":"14","author":"S Prins","year":"2022","unstructured":"Prins S, de Kam ML, Teunissen CE, Groeneveld GJ. Inflammatory plasma biomarkers in subjects with preclinical Alzheimer\u2019s disease. Alzheimers Res Ther. 2022;14:106.","journal-title":"Alzheimers Res Ther"},{"key":"1804_CR58","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1111\/j.1440-1819.1998.tb02706.x","volume":"52","author":"F Muramori","year":"1998","unstructured":"Muramori F, Kobayashi K, Nakamura I. A quantitative study of neurofibrillary tangles, senile plaques and astrocytes in the hippocampal subdivisions and entorhinal cortex in Alzheimer\u2019s disease, normal controls and non-Alzheimer neuropsychiatric diseases. Psychiatry Clin Neurosci. 1998;52:593\u20139.","journal-title":"Psychiatry Clin Neurosci"},{"key":"1804_CR59","doi-asserted-by":"publisher","first-page":"541","DOI":"10.3233\/JAD-2009-1075","volume":"17","author":"S Jesse","year":"2009","unstructured":"Jesse S, Steinacker P, Cepek L, von Arnim CAF, Tumani H, Lehnert S, et al. Glial fibrillary acidic protein and protein S-100B: different concentration pattern of glial proteins in cerebrospinal fluid of patients with Alzheimer\u2019s disease and Creutzfeldt-Jakob disease. J Alzheimers Dis JAD. 2009;17:541\u201351.","journal-title":"J Alzheimers Dis JAD"},{"key":"1804_CR60","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41398-020-01137-1","volume":"11","author":"P Chatterjee","year":"2021","unstructured":"Chatterjee P, Pedrini S, Stoops E, Goozee K, Villemagne VL, Asih PR, et al. Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer\u2019s disease. Transl Psychiatry. 2021;11:27.","journal-title":"Transl Psychiatry"},{"key":"1804_CR61","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1016\/j.neurobiolaging.2008.05.015","volume":"31","author":"JE Simpson","year":"2010","unstructured":"Simpson JE, Ince PG, Lace G, Forster G, Shaw PJ, Matthews F, et al. Astrocyte phenotype in relation to Alzheimer-type pathology in the ageing brain. Neurobiol Aging. 2010;31:578\u201390.","journal-title":"Neurobiol Aging"},{"key":"1804_CR62","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/S1474-4422(21)00361-6","volume":"21","author":"CE Teunissen","year":"2022","unstructured":"Teunissen CE, Verberk IMW, Thijssen EH, Vermunt L, Hansson O, Zetterberg H, et al. Blood-based biomarkers for Alzheimer\u2019s disease: towards clinical implementation. Lancet Neurol. 2022;21:66\u201377.","journal-title":"Lancet Neurol"},{"key":"1804_CR63","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.brainresrev.2009.11.004","volume":"63","author":"MT Heneka","year":"2010","unstructured":"Heneka MT, Rodr\u00edguez JJ, Verkhratsky A. Neuroglia in neurodegeneration. Brain Res Rev. 2010;63:189\u2013211.","journal-title":"Brain Res Rev"},{"key":"1804_CR64","doi-asserted-by":"publisher","first-page":"11231","DOI":"10.1038\/s41598-023-38214-6","volume":"13","author":"C-W Chen","year":"2023","unstructured":"Chen C-W, Kwok Y-T, Cheng Y-T, Huang Y-S, Kuo TBJ, Wu C-H, et al. Reduced slow-wave activity and autonomic dysfunction during sleep precede cognitive deficits in Alzheimer\u2019s disease transgenic mice. Sci Rep. 2023;13:11231.","journal-title":"Sci Rep"},{"key":"1804_CR65","doi-asserted-by":"publisher","first-page":"zsz278","DOI":"10.1093\/sleep\/zsz278","volume":"43","author":"BT Keenan","year":"2020","unstructured":"Keenan BT, Galante RJ, Lian J, Simecek P, Gatti DM, Zhang L, et al. High-throughput sleep phenotyping produces robust and heritable traits in diversity outbred mice and their founder strains. Sleep. 2020;43:zsz278.","journal-title":"Sleep"},{"key":"1804_CR66","doi-asserted-by":"publisher","first-page":"e18726","DOI":"10.7554\/eLife.18726","volume":"5","author":"L Senst","year":"2016","unstructured":"Senst L, Baimoukhametova D, Sterley TL, Bains JS. Sexually dimorphic neuronal responses to social isolation. Elife. 2016;5:e18726.","journal-title":"Elife"},{"key":"1804_CR67","doi-asserted-by":"publisher","first-page":"e0245355","DOI":"10.1371\/journal.pone.0245355","volume":"16","author":"DG Sullens","year":"2021","unstructured":"Sullens DG, Gilley K, Jensen K, Vichaya E, Dolan SL, Sekeres MJ. Social isolation induces hyperactivity and exploration in aged female mice. PLoS ONE. 2021;16:e0245355.","journal-title":"PLoS ONE"},{"key":"1804_CR68","doi-asserted-by":"publisher","first-page":"186","DOI":"10.3389\/fnagi.2019.00186","volume":"11","author":"NR Smalheiser","year":"2019","unstructured":"Smalheiser NR. Ketamine: a neglected therapy for Alzheimer disease. Front Aging Neurosci. 2019;11:186.","journal-title":"Front Aging Neurosci"},{"key":"1804_CR69","doi-asserted-by":"publisher","first-page":"109335","DOI":"10.1016\/j.neuropharm.2022.109335","volume":"224","author":"S Deyama","year":"2023","unstructured":"Deyama S, Kaneda K. Role of neurotrophic and growth factors in the rapid and sustained antidepressant actions of ketamine. Neuropharmacology. 2023;224:109335.","journal-title":"Neuropharmacology"},{"key":"1804_CR70","doi-asserted-by":"publisher","first-page":"eaat8078","DOI":"10.1126\/science.aat8078","volume":"364","author":"RN Moda-Sava","year":"2019","unstructured":"Moda-Sava RN, Murdock MH, Parekh PK, Fetcho RN, Huang BS, Huynh TN, et al. Sustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation. Science. 2019;364:eaat8078.","journal-title":"Science"},{"key":"1804_CR71","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1111\/nmo.13064","volume":"29","author":"V Pauwelyn","year":"2017","unstructured":"Pauwelyn V, Lefebvre RA. 5-HT4 receptors facilitate cholinergic neurotransmission throughout the murine gastrointestinal tract. Neurogastroenterol Motil. 2017;29:173\u2013202.","journal-title":"Neurogastroenterol Motil"},{"key":"1804_CR72","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1136\/gutjnl-2018-317263","volume":"68","author":"N Stakenborg","year":"2019","unstructured":"Stakenborg N, Labeeuw E, Gomez-Pinilla PJ, De Schepper S, Aerts R, Goverse G, et al. Preoperative administration of the 5-HT4 receptor agonist prucalopride reduces intestinal inflammation and shortens postoperative ileus via cholinergic enteric neurons. Gut. 2019;68:1406\u201316.","journal-title":"Gut"},{"key":"1804_CR73","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.nlm.2016.06.014","volume":"138","author":"H Hagena","year":"2017","unstructured":"Hagena H, Manahan-Vaughan D. The serotonergic 5-HT4 receptor: A unique modulator of hippocampal synaptic information processing and cognition. Neurobiol Learn Mem. 2017;138:145\u201353.","journal-title":"Neurobiol Learn Mem"},{"key":"1804_CR74","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.bbrc.2021.03.109","volume":"556","author":"Y Shi","year":"2021","unstructured":"Shi Y, Qiao C-M, Zhou Y, Wu J, Cui C, Hong H, et al. Protective effects of prucalopride in MPTP-induced Parkinson\u2019s disease mice: neurochemistry, motor function and gut barrier. Biochem Biophys Res Commun. 2021;556:16\u201322.","journal-title":"Biochem Biophys Res Commun"},{"key":"1804_CR75","doi-asserted-by":"publisher","first-page":"87","DOI":"10.3892\/ijmm.2022.5143","volume":"50","author":"Y Wang","year":"2022","unstructured":"Wang Y, Xu X, Lin L. Prucalopride might improve intestinal motility by promoting the regeneration of the enteric nervous system in diabetic rats. Int J Mol Med. 2022;50:87.","journal-title":"Int J Mol Med"},{"key":"1804_CR76","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1038\/s41582-021-00616-3","volume":"18","author":"A Abdelhak","year":"2022","unstructured":"Abdelhak A, Foschi M, Abu-Rumeileh S, Yue JK, D\u2019Anna L, Huss A, et al. Blood GFAP as an emerging biomarker in brain and spinal cord disorders. Nat Rev Neurol. 2022;18:158\u201372.","journal-title":"Nat Rev Neurol"},{"key":"1804_CR77","doi-asserted-by":"publisher","first-page":"102970","DOI":"10.1016\/j.conb.2025.102970","volume":"90","author":"A Derevyanko","year":"2025","unstructured":"Derevyanko A, Tao T, Allen NJ. Common alterations to astrocytes across neurodegenerative disorders. Curr Opin Neurobiol. 2025;90:102970.","journal-title":"Curr Opin Neurobiol"},{"key":"1804_CR78","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1093\/brain\/awae104","volume":"147","author":"C Limberger","year":"2024","unstructured":"Limberger C, Zimmer ER. Blood GFAP reflects astrocyte reactivity to Alzheimer\u2019s pathology in post-mortem brain tissue. Brain J Neurol. 2024;147:1598\u2013600.","journal-title":"Brain J Neurol"},{"key":"1804_CR79","doi-asserted-by":"publisher","first-page":"1667","DOI":"10.1093\/brain\/awae035","volume":"147","author":"P S\u00e1nchez-Juan","year":"2024","unstructured":"S\u00e1nchez-Juan P, Valeriano-Lorenzo E, Ruiz-Gonz\u00e1lez A, Pastor AB, Rodrigo Lara H, L\u00f3pez-Gonz\u00e1lez F, et al. Serum GFAP levels correlate with astrocyte reactivity, post-mortem brain atrophy and neurofibrillary tangles. Brain J Neurol. 2024;147:1667\u201379.","journal-title":"Brain J Neurol"},{"key":"1804_CR80","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s00401-024-02828-5","volume":"148","author":"JM Phillips","year":"2024","unstructured":"Phillips JM, Winfree RL, Seto M, Schneider JA, Bennett DA, Dumitrescu LC, et al. Pathologic and clinical correlates of region-specific brain GFAP in Alzheimer\u2019s disease. Acta Neuropathol (Berl). 2024;148:69.","journal-title":"Acta Neuropathol (Berl)"},{"key":"1804_CR81","doi-asserted-by":"publisher","first-page":"114","DOI":"10.3389\/fnagi.2018.00114","volume":"10","author":"BG Perez-Nievas","year":"2018","unstructured":"Perez-Nievas BG, Serrano-Pozo A. Deciphering the astrocyte reaction in Alzheimer\u2019s disease. Front Aging Neurosci. 2018;10:114.","journal-title":"Front Aging Neurosci"},{"key":"1804_CR82","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.1038\/s41591-023-02380-x","volume":"29","author":"B Bellaver","year":"2023","unstructured":"Bellaver B, Povala G, Ferreira PCL, Ferrari-Souza JP, Leffa DT, Lussier FZ, et al. Astrocyte reactivity influences amyloid-\u03b2 effects on tau pathology in preclinical Alzheimer\u2019s disease. Nat Med. 2023;29:1775\u201381.","journal-title":"Nat Med"},{"key":"1804_CR83","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.bbrc.2022.03.068","volume":"616","author":"X Ma","year":"2022","unstructured":"Ma X, Yang S, Zhang Z, Liu L, Shi W, Yang S, et al. Rapid and sustained restoration of astrocytic functions by ketamine in depression model mice. Biochem Biophys Res Commun. 2022;616:89\u201394.","journal-title":"Biochem Biophys Res Commun"},{"key":"1804_CR84","doi-asserted-by":"publisher","first-page":"2049","DOI":"10.1007\/s12035-023-03669-1","volume":"61","author":"G Wen","year":"2024","unstructured":"Wen G, Zhan X, Xu X, Xia X, Jiang S, Ren X, et al. Ketamine improves the glymphatic pathway by reducing the pyroptosis of hippocampal astrocytes in the chronic unpredictable mild stress model. Mol Neurobiol. 2024;61:2049\u201362.","journal-title":"Mol Neurobiol"},{"key":"1804_CR85","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1016\/j.cell.2019.04.001","volume":"177","author":"MS Ioannou","year":"2019","unstructured":"Ioannou MS, Jackson J, Sheu S-H, Chang C-L, Weigel AV, Liu H, et al. Neuron-astrocyte metabolic coupling protects against activity-induced fatty acid toxicity. Cell. 2019;177:1522-1535.e14.","journal-title":"Cell"},{"key":"1804_CR86","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/j.cmet.2011.08.016","volume":"14","author":"M B\u00e9langer","year":"2011","unstructured":"B\u00e9langer M, Allaman I, Magistretti PJ. Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab. 2011;14:724\u201338.","journal-title":"Cell Metab"},{"key":"1804_CR87","doi-asserted-by":"publisher","first-page":"668517","DOI":"10.3389\/fendo.2021.668517","volume":"12","author":"P Mulica","year":"2021","unstructured":"Mulica P, Gr\u00fcnewald A, Pereira SL. Astrocyte-neuron metabolic crosstalk in neurodegeneration: a mitochondrial perspective. Front Endocrinol. 2021;12:668517.","journal-title":"Front Endocrinol"},{"key":"1804_CR88","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.1016\/j.cmet.2021.07.006","volume":"33","author":"G Bonvento","year":"2021","unstructured":"Bonvento G, Bola\u00f1os JP. Astrocyte-neuron metabolic cooperation shapes brain activity. Cell Metab. 2021;33:1546\u201364.","journal-title":"Cell Metab"},{"key":"1804_CR89","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1038\/s41586-023-07011-6","volume":"627","author":"W Sun","year":"2024","unstructured":"Sun W, Liu Z, Jiang X, Chen MB, Dong H, Liu J, et al. Spatial transcriptomics reveal neuron-astrocyte synergy in long-term memory. Nature. 2024;627:374\u201381.","journal-title":"Nature"},{"key":"1804_CR90","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.tins.2010.12.001","volume":"34","author":"I Allaman","year":"2011","unstructured":"Allaman I, B\u00e9langer M, Magistretti PJ. Astrocyte-neuron metabolic relationships: for better and for worse. Trends Neurosci. 2011;34:76\u201387.","journal-title":"Trends Neurosci"},{"key":"1804_CR91","doi-asserted-by":"publisher","first-page":"106255","DOI":"10.1016\/j.nbd.2023.106255","volume":"185","author":"Z Jiwaji","year":"2023","unstructured":"Jiwaji Z, Hardingham GE. The consequences of neurodegenerative disease on neuron-astrocyte metabolic and redox interactions. Neurobiol Dis. 2023;185:106255.","journal-title":"Neurobiol Dis"},{"key":"1804_CR92","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1038\/s41467-023-37240-2","volume":"14","author":"A Lia","year":"2023","unstructured":"Lia A, Sansevero G, Chiavegato A, Sbrissa M, Pendin D, Mariotti L, et al. Rescue of astrocyte activity by the calcium sensor STIM1 restores long-term synaptic plasticity in female mice modelling Alzheimer\u2019s disease. Nat Commun. 2023;14:1590.","journal-title":"Nat Commun"},{"key":"1804_CR93","doi-asserted-by":"publisher","first-page":"4595","DOI":"10.1111\/bph.12710","volume":"171","author":"N Kokras","year":"2014","unstructured":"Kokras N, Dalla C. Sex differences in animal models of psychiatric disorders. Br J Pharmacol. 2014;171:4595\u2013619.","journal-title":"Br J Pharmacol"},{"key":"1804_CR94","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/npp.2016.174","volume":"42","author":"AA Keiser","year":"2017","unstructured":"Keiser AA, Turnbull LM, Darian MA, Feldman DE, Song I, Tronson NC. Sex differences in context fear generalization and recruitment of hippocampus and amygdala during retrieval. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2017;42:397\u2013407.","journal-title":"Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol"},{"key":"1804_CR95","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1038\/sj.npp.1301533","volume":"33","author":"C Dalla","year":"2008","unstructured":"Dalla C, Edgecomb C, Whetstone AS, Shors TJ. Females do not express learned helplessness like males do. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2008;33:1559\u201369.","journal-title":"Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol"},{"key":"1804_CR96","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/2045-5380-2-7","volume":"2","author":"K Lebron-Milad","year":"2012","unstructured":"Lebron-Milad K, Abbs B, Milad MR, Linnman C, Rougemount-B\u00fccking A, Zeidan MA, et al. Sex differences in the neurobiology of fear conditioning and extinction: a preliminary fMRI study of shared sex differences with stress-arousal circuitry. Biol Mood Anxiety Disord. 2012;2:7.","journal-title":"Biol Mood Anxiety Disord"},{"key":"1804_CR97","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.yhbeh.2015.04.002","volume":"76","author":"LY Maeng","year":"2015","unstructured":"Maeng LY, Milad MR. Sex differences in anxiety disorders: interactions between fear, stress, and gonadal hormones. Horm Behav. 2015;76:106\u201317.","journal-title":"Horm Behav"},{"key":"1804_CR98","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1002\/hbm.22683","volume":"36","author":"L Kogler","year":"2015","unstructured":"Kogler L, Gur RC, Derntl B. Sex differences in cognitive regulation of psychosocial achievement stress: brain and behavior. Hum Brain Mapp. 2015;36:1028\u201342.","journal-title":"Hum Brain Mapp"},{"key":"1804_CR99","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1016\/j.tem.2023.06.003","volume":"34","author":"AW Fleischer","year":"2023","unstructured":"Fleischer AW, Frick KM. New perspectives on sex differences in learning and memory. Trends Endocrinol Metab TEM. 2023;34:526\u201338.","journal-title":"Trends Endocrinol Metab TEM"},{"key":"1804_CR100","doi-asserted-by":"publisher","first-page":"109298","DOI":"10.1016\/j.neuropharm.2022.109298","volume":"222","author":"EP Bauer","year":"2023","unstructured":"Bauer EP. Sex differences in fear responses: neural circuits. Neuropharmacology. 2023;222:109298.","journal-title":"Neuropharmacology"},{"key":"1804_CR101","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1124\/jpet.118.251652","volume":"367","author":"SK Saland","year":"2018","unstructured":"Saland SK, Kabbaj M. Sex differences in the pharmacokinetics of low-dose ketamine in plasma and brain of male and female rats. J Pharmacol Exp Ther. 2018;367:393\u2013404.","journal-title":"J Pharmacol Exp Ther"},{"key":"1804_CR102","doi-asserted-by":"publisher","first-page":"797","DOI":"10.5414\/CP201769","volume":"50","author":"X Chen","year":"2012","unstructured":"Chen X, Jiang J, Liu T, Liu H, Zhong W, Hu P. Pharmacokinetics of single and repeated oral doses prucalopride in healthy Chinese volunteers. Int J Clin Pharmacol Ther. 2012;50:797\u2013804.","journal-title":"Int J Clin Pharmacol Ther"},{"key":"1804_CR103","doi-asserted-by":"crossref","unstructured":"Chen BK, Whye A, Matthews LC, Moniz T, Mendez-David I, Gardier AM, et al. Chronic, combinatorial targeting of NMDARs and 5-HT4Rs exerts extended behavioral effects against stress-induced perseverative behavior and hyponeophagia. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol. 2025.","DOI":"10.1038\/s41386-025-02107-1"},{"key":"1804_CR104","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1177\/0269881120959644","volume":"35","author":"LA Jelen","year":"2021","unstructured":"Jelen LA, Young AH, Stone JM. Ketamine: A tale of two enantiomers. J Psychopharmacol Oxf Engl. 2021;35:109\u201323.","journal-title":"J Psychopharmacol Oxf Engl"},{"key":"1804_CR105","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1001\/jamapsychiatry.2019.1189","volume":"76","author":"EJ Daly","year":"2019","unstructured":"Daly EJ, Trivedi MH, Janik A, Li H, Zhang Y, Li X, et al. Efficacy of esketamine nasal spray plus oral antidepressant treatment for relapse prevention in patients with treatment-resistant depression: a randomized clinical trial. JAMA Psychiat. 2019;76:893\u2013903.","journal-title":"JAMA Psychiat"},{"key":"1804_CR106","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1001\/jamapsychiatry.2017.3739","volume":"75","author":"EJ Daly","year":"2018","unstructured":"Daly EJ, Singh JB, Fedgchin M, Cooper K, Lim P, Shelton RC, et al. Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: a randomized clinical trial. JAMA Psychiat. 2018;75:139\u201348.","journal-title":"JAMA Psychiat"},{"key":"1804_CR107","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1093\/ijnp\/pyz039","volume":"22","author":"M Fedgchin","year":"2019","unstructured":"Fedgchin M, Trivedi M, Daly EJ, Melkote R, Lane R, Lim P, et al. Efficacy and safety of fixed-dose esketamine nasal spray combined with a new oral antidepressant in treatment-resistant depression: results of a randomized, double-blind, active-controlled study (TRANSFORM-1). Int J Neuropsychopharmacol. 2019;22:616\u201330.","journal-title":"Int J Neuropsychopharmacol"},{"key":"1804_CR108","doi-asserted-by":"publisher","first-page":"19m13191","DOI":"10.4088\/JCP.19m13191","volume":"81","author":"DJ Fu","year":"2020","unstructured":"Fu DJ, Ionescu DF, Li X, Lane R, Lim P, Sanacora G, et al. Esketamine nasal spray for rapid reduction of major depressive disorder symptoms in patients who have active suicidal ideation with intent: double-blind, randomized study (ASPIRE I). J Clin Psychiatry. 2020;81:19m13191.","journal-title":"J Clin Psychiatry"},{"key":"1804_CR109","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1093\/ijnp\/pyaa068","volume":"24","author":"DF Ionescu","year":"2021","unstructured":"Ionescu DF, Fu D-J, Qiu X, Lane R, Lim P, Kasper S, et al. Esketamine nasal spray for rapid reduction of depressive symptoms in patients with major depressive disorder who have active suicide ideation with intent: results of a phase 3, double-blind, randomized study (ASPIRE II). Int J Neuropsychopharmacol. 2021;24:22\u201331.","journal-title":"Int J Neuropsychopharmacol"},{"key":"1804_CR110","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.jagp.2019.10.008","volume":"28","author":"R Ochs-Ross","year":"2020","unstructured":"Ochs-Ross R, Daly EJ, Zhang Y, Lane R, Lim P, Morrison RL, et al. Efficacy and safety of esketamine nasal spray plus an oral antidepressant in elderly patients with treatment-resistant depression-TRANSFORM-3. Am J Geriatr Psychiatry. 2020;28:121\u201341.","journal-title":"Am J Geriatr Psychiatry"},{"key":"1804_CR111","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1176\/appi.ajp.2019.19020172","volume":"176","author":"V Popova","year":"2019","unstructured":"Popova V, Daly EJ, Trivedi M, Cooper K, Lane R, Lim P, et al. Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: a randomized double-blind active-controlled study. Am J Psychiatry. 2019;176:428\u201338.","journal-title":"Am J Psychiatry"},{"key":"1804_CR112","doi-asserted-by":"publisher","first-page":"19m12891","DOI":"10.4088\/JCP.19m12891","volume":"81","author":"E Wajs","year":"2020","unstructured":"Wajs E, Aluisio L, Holder R, Daly EJ, Lane R, Lim P, et al. Esketamine nasal spray plus oral antidepressant in patients with treatment-resistant depression: assessment of long-term safety in a phase 3, open-label study (SUSTAIN-2). J Clin Psychiatry. 2020;81:19m12891.","journal-title":"J Clin Psychiatry"},{"key":"1804_CR113","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1038\/s41386-023-01577-5","volume":"48","author":"N Zaki","year":"2023","unstructured":"Zaki N, Chen LN, Lane R, Doherty T, Drevets WC, Morrison RL, et al. Long-term safety and maintenance of response with esketamine nasal spray in participants with treatment-resistant depression: interim results of the SUSTAIN-3 study. Neuropsychopharmacology. 2023;48:1225\u201333.","journal-title":"Neuropsychopharmacology"},{"key":"1804_CR114","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nature17998","volume":"533","author":"P Zanos","year":"2016","unstructured":"Zanos P, Moaddel R, Morris PJ, Georgiou P, Fischell J, Elmer GI, et al. NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature. 2016;533:481\u20136.","journal-title":"Nature"},{"key":"1804_CR115","doi-asserted-by":"publisher","first-page":"109345","DOI":"10.1016\/j.neuropharm.2022.109345","volume":"224","author":"BK Chen","year":"2023","unstructured":"Chen BK, Denny CA. Weapons of stress reduction: (R,S)-ketamine and its metabolites as prophylactics for the prevention of stress-induced psychiatric disorders. Neuropharmacology. 2023;224:109345.","journal-title":"Neuropharmacology"},{"key":"1804_CR116","doi-asserted-by":"publisher","first-page":"109219","DOI":"10.1016\/j.neuropharm.2022.109219","volume":"218","author":"J-C Zhang","year":"2022","unstructured":"Zhang J-C, Yao W, Hashimoto K. Arketamine, a new rapid-acting antidepressant: a historical review and future directions. Neuropharmacology. 2022;218:109219.","journal-title":"Neuropharmacology"},{"key":"1804_CR117","doi-asserted-by":"publisher","first-page":"2283","DOI":"10.3390\/biomedicines12102283","volume":"12","author":"P Kawczak","year":"2024","unstructured":"Kawczak P, Feszak I, B\u0105czek T. Ketamine, esketamine, and arketamine: their mechanisms of action and applications in the treatment of depression and alleviation of depressive symptoms. Biomedicines. 2024;12:2283.","journal-title":"Biomedicines"},{"key":"1804_CR118","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.jpsychires.2023.06.028","volume":"164","author":"ID Bandeira","year":"2023","unstructured":"Bandeira ID, Leal GC, Correia-Melo FS, Souza-Marques B, Silva SS, Lins-Silva DH, et al. Arketamine for bipolar depression: open-label, dose-escalation, pilot study. J Psychiatr Res. 2023;164:229\u201334.","journal-title":"J Psychiatr Res"},{"key":"1804_CR119","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/j.jad.2024.08.222","volume":"367","author":"D Xu","year":"2024","unstructured":"Xu D, Liu G, Zhao M, Wan X, Qu Y, Murayama R, et al. Effects of arketamine on depression-like behaviors and demyelination in mice exposed to chronic restrain stress: A role of transforming growth factor-\u03b21. J Affect Disord. 2024;367:745\u201355.","journal-title":"J Affect Disord"},{"key":"1804_CR120","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1007\/s00406-020-01110-5","volume":"271","author":"GC Leal","year":"2021","unstructured":"Leal GC, Bandeira ID, Correia-Melo FS, Telles M, Mello RP, Vieira F, et al. Intravenous arketamine for treatment-resistant depression: open-label pilot study. Eur Arch Psychiatry Clin Neurosci. 2021;271:577\u201382.","journal-title":"Eur Arch Psychiatry Clin Neurosci"},{"key":"1804_CR121","doi-asserted-by":"publisher","first-page":"6804","DOI":"10.3390\/ijms25126804","volume":"25","author":"H Shafique","year":"2024","unstructured":"Shafique H, Demers JC, Biesiada J, Golani LK, Cerne R, Smith JL, et al. (R)-(-)-Ketamine: the promise of a novel treatment for psychiatric and neurological disorders. Int J Mol Sci. 2024;25:6804.","journal-title":"Int J Mol Sci"},{"key":"1804_CR122","doi-asserted-by":"publisher","first-page":"137836","DOI":"10.1016\/j.neulet.2024.137836","volume":"834","author":"Y Tu","year":"2024","unstructured":"Tu Y, Xu B. Esketamine induces tripartite motif-containing protein 24 to improve cognitive dysfunction in Alzheimer\u2019s disease. Neurosci Lett. 2024;834:137836.","journal-title":"Neurosci Lett"},{"key":"1804_CR123","doi-asserted-by":"publisher","first-page":"104762","DOI":"10.1016\/j.neubiorev.2022.104762","volume":"139","author":"X Wang","year":"2022","unstructured":"Wang X, Yang J, Hashimoto K. (R)-ketamine as prophylactic and therapeutic drug for neurological disorders: Beyond depression. Neurosci Biobehav Rev. 2022;139:104762.","journal-title":"Neurosci Biobehav Rev"},{"key":"1804_CR124","doi-asserted-by":"publisher","first-page":"106209","DOI":"10.1016\/j.neubiorev.2025.106209","volume":"174","author":"R Murayama","year":"2025","unstructured":"Murayama R, Cai Y, Nakamura H, Hashimoto K. Demyelination in psychiatric and neurological disorders: Mechanisms, clinical impact, and novel therapeutic strategies. Neurosci Biobehav Rev. 2025;174:106209.","journal-title":"Neurosci Biobehav Rev"},{"key":"1804_CR125","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1007\/s00441-007-0432-4","volume":"329","author":"O von Bohlen Und Halbach","year":"2007","unstructured":"von Bohlen Und Halbach O. Immunohistological markers for staging neurogenesis in adult hippocampus. Cell Tissue Res. 2007;329:409\u201320.","journal-title":"Cell Tissue Res"},{"key":"1804_CR126","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1002\/hipo.20964","volume":"22","author":"CA Denny","year":"2012","unstructured":"Denny CA, Burghardt NS, Schachter DM, Hen R, Drew MR. 4- to 6-week-old adult-born hippocampal neurons influence novelty-evoked exploration and contextual fear conditioning. Hippocampus. 2012;22:1188\u2013201.","journal-title":"Hippocampus"}],"container-title":["Alzheimer's Research & Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13195-025-01804-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13195-025-01804-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13195-025-01804-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,7]],"date-time":"2025-09-07T12:34:59Z","timestamp":1757248499000},"score":1,"resource":{"primary":{"URL":"https:\/\/alzres.biomedcentral.com\/articles\/10.1186\/s13195-025-01804-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,15]]},"references-count":126,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["1804"],"URL":"https:\/\/doi.org\/10.1186\/s13195-025-01804-9","relation":{},"ISSN":["1758-9193"],"issn-type":[{"value":"1758-9193","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,15]]},"assertion":[{"value":"29 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All procedures were conducted in accordance with the National Institutes of Health (NIH)\u00a0regulations and by the Institutional Animal Care and Use Committees (IACUCs) of Columbia University Irving Medical Center (CUIMC) and the Research Foundation for Mental Hygiene, Inc. (RFMH) at the New York State Psychiatric Institute (NYSPI).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"BKC, HCH, and CAD are named on provisional patent applications for the prophylactic use of (\n                      R\n                      ,\n                      S\n                      )-ketamine, 5-HT\n                      4\n                      R agonists, and other compounds against stress-related psychiatric disorders and Alzheimer\u2019s disease. SJ is employed by Silo Pharma, and EW is founder and Chief Executive Officer of Silo Pharma. AW, LCM, AY, MJW, and RL have no conflicts of interest to disclose.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"160"}}