{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T13:47:37Z","timestamp":1782481657948,"version":"3.54.5"},"reference-count":50,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Fondo de Cooperaci\u00f3n Triangular Uni\u00f3n Europea-Cuba-Am\u00e9rica Latina y el Caribe","award":["N\u00ba 3058392, ADELANTE, AECID, Ministerio de Asunto"],"award-info":[{"award-number":["N\u00ba 3058392, ADELANTE, AECID, Ministerio de Asunto"]}]},{"name":"PHC Carlos J. Finlay program from Campus France","award":["47069SA and 53299ZK"],"award-info":[{"award-number":["47069SA and 53299ZK"]}]},{"name":"SIGMA-1 EUROPA COST Action","award":["CA23156"],"award-info":[{"award-number":["CA23156"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Amylovis-201 (CNEURO-201) shows strong neuroprotective activity in Alzheimer\u2019s disease (AD) models due to its anti-A\u03b2 aggregating properties and sigma-1 receptors (S1R) agonist activity. The drug is neuroprotective in transgenic rodent models of AD that could translate into disease-modifying effects by both protecting neuronal and glial viability and actively decreasing amyloid aggregation. The individual vulnerability to the neurodegenerative process in AD is highly dependent on the \u201ccognitive reserve,\u201d understood as the efficacy of brain plasticity throughout lifetime events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>We aimed to determine whether Amylovis-201 efficacy in AD could be potentiated through stimulation of cognitive reserve. We combined Amylovis-201 administration with an experimental model of environmental enrichment (EE), using training on the Hamlet device. We analyzed the potentiating effects of the combination on brain plasticity and the development of resilience against memory deficits in a pharmacological AD model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We implemented a combined protocol with repeated per os (PO) administration of Amylovis-201 (0.1 and 1\u2009mg\/kg) and EE over 2\u2009weeks (5\u2009days\/week), consisting of a 4-hour exploration of the Hamlet, a complex environment mimicking a small village with five functionalized houses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The combination of EE and low dose (0.1\u2009mg\/kg PO) of Amylovis-201 had an additive effect on hippocampal neurogenesis. It also protected mice against scopolamine (0.5\u2009mg\/kg IP)-induced spatial working memory deficits in the Y-maze and, at 0.1 or 1\u2009mg\/kg PO, against A\u03b2\n                      <jats:sub>25\u201335<\/jats:sub>\n                      -induced memory deficits.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>As EE is known to increase S1R expression, the combination of EE and Amylovis-201 had major effects on brain plasticity and neuroprotection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/02698811261458343","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T08:55:28Z","timestamp":1782291328000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhanced cognitive protection through the combination of Amylovis-201, an anti-amyloidogenic agent with sigma-1 receptor agonist activity, and environmental enrichment in mice"],"prefix":"10.1177","author":[{"given":"Roberto","family":"Men\u00e9ndez Soto del Valle","sequence":"first","affiliation":[{"name":"Department of Neurochemistry, Cuban Center for Neurosciences, Cubanacan, Playa, Havana, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlyne","family":"Barry-Simonnet","sequence":"additional","affiliation":[{"name":"MMDN, EPHE, INSERM, University of Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lison","family":"Verjus","sequence":"additional","affiliation":[{"name":"MMDN, EPHE, INSERM, University of Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Crouzier","sequence":"additional","affiliation":[{"name":"MMDN, EPHE, INSERM, University of Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sairys","family":"Pe\u00f1a Alcolea","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, Cuban Center for Neurosciences, Cubanacan, Playa, Havana, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marquiza","family":"Sabl\u00f3n Carrazana","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, Cuban Center for Neurosciences, Cubanacan, Playa, Havana, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4074-6793","authenticated-orcid":false,"given":"Tangui","family":"Maurice","sequence":"additional","affiliation":[{"name":"MMDN, EPHE, INSERM, University of Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chryslaine","family":"Rodr\u00edguez-Tanty","sequence":"additional","affiliation":[{"name":"Department of Neurochemistry, Cuban Center for Neurosciences, Cubanacan, Playa, Havana, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"crossref","unstructured":"Alonso G Phan V Guillemain I et al. (2000) Immunocytochemical localization of the sigma1 receptor in the adult rat central nervous system. Neuroscience 97(1): 155\u2013170. https:\/\/doi.org\/10.1016\/s0306-4522(00)00014-2","DOI":"10.1016\/S0306-4522(00)00014-2"},{"key":"e_1_3_2_3_1","doi-asserted-by":"crossref","unstructured":"Arai JA Feig LA (2011) Long-lasting and transgenerational effects of an environmental enrichment on memory formation. Brain Research Bulletin 85(1\u20132): 30\u201335. https:\/\/doi.org\/10.1016\/j.brainresbull.2010.11.003","DOI":"10.1016\/j.brainresbull.2010.11.003"},{"key":"e_1_3_2_4_1","doi-asserted-by":"crossref","unstructured":"Arendash GW Garcia MF Costa DA et al. (2004) Environmental enrichment improves cognition in aged Alzheimer\u2019s transgenic mice despite stable b-amyloid deposition. Neuroreport 15(11): 1751\u20131754. https:\/\/doi.org\/10.1097\/01.wnr.0000137183.68847.4e","DOI":"10.1097\/01.wnr.0000137183.68847.4e"},{"key":"e_1_3_2_5_1","doi-asserted-by":"crossref","unstructured":"Branchi I Francia N Alleva E (2004) Epigenetic control of neurobehavioural plasticity: The role of neurotrophins. Behavioural Pharmacology 15(5\u20136): 353\u2013362. https:\/\/doi.org\/10.1097\/00008877-200409000-00006","DOI":"10.1097\/00008877-200409000-00006"},{"key":"e_1_3_2_6_1","doi-asserted-by":"crossref","unstructured":"Canet G Zussy C Hernandez C et al. (2023) The pathomimetic oA\u03b225\u201335 model of Alzheimer\u2019s disease: Potential for screening of new therapeutic agents. Pharmacology & Therapeutics 245: 108398. https:\/\/doi.org\/10.1016\/j.pharmthera.2023.108398","DOI":"10.1016\/j.pharmthera.2023.108398"},{"key":"e_1_3_2_7_1","doi-asserted-by":"crossref","unstructured":"Carles A Freyssin A Guehairia S et al. (2025) Neuroprotection by chronic administration of Fluoroethylnormemantine (FENM) in mouse models of Alzheimer\u2019s disease. Alzheimer\u2019s Research & Therapy 17(1): 7. https:\/\/doi.org\/10.1186\/s13195-024-01648-9","DOI":"10.1186\/s13195-024-01648-9"},{"key":"e_1_3_2_8_1","doi-asserted-by":"crossref","unstructured":"Chumakov I Nabirotchkin S Cholet N et al. (2015) Combining two repurposed drugs as a promising approach for Alzheimer\u2019s disease therapy. Scientific Reports 5: 7608. https:\/\/doi.org\/10.1038\/srep07608","DOI":"10.1038\/srep07608"},{"key":"e_1_3_2_9_1","doi-asserted-by":"crossref","unstructured":"Crouzier L Maurice T (2018) Assessment of topographic memory in mice in a complex environment using the Hamlet test. Current Protocols in Mouse Biology 8(2): e43. https:\/\/doi.org\/10.1002\/cpmo.43","DOI":"10.1002\/cpmo.43"},{"key":"e_1_3_2_10_1","doi-asserted-by":"crossref","unstructured":"Crouzier L Gilabert D Rossel M et al. (2018) Topographical memory analyzed in mice using the Hamlet Test a novel complex maze. Neurobiology of Learning and Memory 149: 118\u2013134. https:\/\/doi.org\/10.1016\/j.nlm.2018.02.014","DOI":"10.1016\/j.nlm.2018.02.014"},{"key":"e_1_3_2_11_1","doi-asserted-by":"crossref","unstructured":"Crouzier L Couly S Roques C et al. (2020) Sigma-1 (\u03c31) receptor activity is necessary for physiological brain plasticity in mice. European Neuropsychopharmacology 39: 29\u201345. https:\/\/doi.org\/10.1016\/j.euroneuro.2020.08.010","DOI":"10.1016\/j.euroneuro.2020.08.010"},{"key":"e_1_3_2_12_1","doi-asserted-by":"crossref","unstructured":"During MJ Cao L (2006) VEGF a mediator of the effect of experience on hippocampal neurogenesis. Current Alzheimer Research 3(1): 29\u201333. https:\/\/doi.org\/10.2174\/156720506775697133","DOI":"10.2174\/156720506775697133"},{"key":"e_1_3_2_13_1","doi-asserted-by":"crossref","unstructured":"Est\u00e9vez-Silva HM Cuesto G Romero N et al. (2022) Pridopidine promotes synaptogenesis and reduces spatial memory deficits in the Alzheimer\u2019s disease APP\/PS1 mouse model. Neurotherapeutics 19(5): 1566\u20131587. https:\/\/doi.org\/10.1007\/s13311-022-01280-1","DOI":"10.1007\/s13311-022-01280-1"},{"key":"e_1_3_2_14_1","doi-asserted-by":"crossref","unstructured":"Fisher A Bezprozvanny I Wu L et al. (2016) AF710B a novel M1\/\u03c31 agonist with therapeutic efficacy in animal models of Alzheimer\u2019s disease. Neurodegenerative Diseases 16(1\u20132): 95\u2013110. https:\/\/doi.org\/10.1159\/000440864","DOI":"10.1159\/000440864"},{"key":"e_1_3_2_15_1","doi-asserted-by":"crossref","unstructured":"Gage FH (2025) Adult neurogenesis in the human dentate gyrus. Hippocampus 35(1): e23655. https:\/\/doi.org\/10.1002\/hipo.23655","DOI":"10.1002\/hipo.23655"},{"key":"e_1_3_2_16_1","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Pupo L Crouzier L Bencomo-Mart\u00ednez A et al. (2024) Amylovis-201 is a new dual-target ligand acting as an anti-amyloidogenic compound and a potent agonist of the \u03c31 chaperone protein. Acta Pharmaceutica Sinica B 14(10): 4345\u20134359. https:\/\/doi.org\/10.1016\/j.apsb.2024.06.013","DOI":"10.1016\/j.apsb.2024.06.013"},{"key":"e_1_3_2_17_1","doi-asserted-by":"crossref","unstructured":"Haley TJ McCormick WG (1957) Pharmacological effects produced by intracerebral injection of drugs in the conscious mouse. British Journal of Pharmacology 12(1): 12\u201315. https:\/\/doi.org\/10.1111\/j.1476-5381.1957.tb01354.x","DOI":"10.1111\/j.1476-5381.1957.tb01354.x"},{"key":"e_1_3_2_18_1","doi-asserted-by":"crossref","unstructured":"Hall H Iulita MF Gubert P et al. (2018) AF710B an M1\/sigma-1 receptor agonist with long-lasting disease-modifying properties in a transgenic rat model of Alzheimer\u2019s disease. Alzheimer\u2019s & Dementia 14(6): 811\u2013823. https:\/\/doi.org\/10.1016\/j.jalz.2017.11.009","DOI":"10.1016\/j.jalz.2017.11.009"},{"key":"e_1_3_2_19_1","doi-asserted-by":"crossref","unstructured":"Hampel H Williams C Etcheto A et al. (2020) A precision medicine framework using artificial intelligence for the identification and confirmation of genomic biomarkers of response to an Alzheimer\u2019s disease therapy: Analysis of the blarcamesine (ANAVEX2-73) Phase 2a clinical study. Alzheimers Dement (NY) 6(1): e12013. https:\/\/doi.org\/10.1002\/trc2.12013","DOI":"10.1002\/trc2.12013"},{"key":"e_1_3_2_20_1","doi-asserted-by":"crossref","unstructured":"Hayashi T Su TP (2007) Sigma-1 receptor chaperones at the ER-mitochondrion interface regulate Ca2+ signaling and cell survival. Cell 131(3): 596\u2013610. https:\/\/doi.org\/10.1016\/j.cell.2007.08.036","DOI":"10.1016\/j.cell.2007.08.036"},{"key":"e_1_3_2_21_1","doi-asserted-by":"crossref","unstructured":"Hayashi T Maurice T Su TP (2000) Ca2+ signaling via sigma1-receptors: Novel regulatory mechanism affecting intracellular Ca2+ concentration. Journal of Pharmacology and Experimental Therapeutics 293(3): 788\u2013798. https:\/\/doi.org\/10.1016\/S0022-3565(24)39299-7","DOI":"10.1016\/S0022-3565(24)39299-7"},{"key":"e_1_3_2_22_1","doi-asserted-by":"crossref","unstructured":"Hung AS Liang Y Chow TC et al. (2016) Mutated tau amyloid and neuroinflammation in Alzheimer disease-A brief review. Progress in Histochemistry and Cytochemistry 51(1): 1\u20138. https:\/\/doi.org\/10.1016\/j.proghi.2016.01.001","DOI":"10.1016\/j.proghi.2016.01.001"},{"key":"e_1_3_2_23_1","doi-asserted-by":"crossref","unstructured":"Kempermann G Kuhn HG Gage FH (1997) More hippocampal neurons in adult mice living in an enriched environment. Nature 386(6624): 493\u2013495. https:\/\/doi.org\/10.1038\/386493a0","DOI":"10.1038\/386493a0"},{"key":"e_1_3_2_24_1","doi-asserted-by":"crossref","unstructured":"Kilkenny C Browne W Cuthill IC et al. (2010) Animal research: Reporting in vivo experiments: The ARRIVE guidelines. British Journal of Pharmacology 160(7): 1577\u20131579. https:\/\/doi.org\/10.1111\/j.1476-5381.2010.00872.x","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_3_2_25_1","doi-asserted-by":"crossref","unstructured":"Lahmy V Meunier J Malmstr\u00f6m S et al. (2013) Blockade of Tau hyperphosphorylation and A\u03b21-42 generation by the aminotetrahydrofuran derivative ANAVEX2-73 a mixed muscarinic and \u03c31 receptor agonist in a nontransgenic mouse model of Alzheimer\u2019s disease. Neuropsychopharmacology 38(9): 1706\u20131723. https:\/\/doi.org\/10.1038\/npp.2013.70","DOI":"10.1038\/npp.2013.70"},{"key":"e_1_3_2_26_1","doi-asserted-by":"crossref","unstructured":"Lazarov O Robinson J Tang YP et al. (2005) Environmental enrichment reduces Ab levels and amyloid deposition in transgenic mice. Cell 120(5): 701\u2013713. https:\/\/doi.org\/10.1016\/j.cell.2005.01.015","DOI":"10.1016\/j.cell.2005.01.015"},{"key":"e_1_3_2_27_1","doi-asserted-by":"crossref","unstructured":"Li L Xu B Zhu Y et al. (2010) DHEA prevents A\u03b225-35-impaired survival of newborn neurons in the dentate gyrus through a modulation of PI3K-Akt-mTOR signaling. Neuropharmacology 59(4\u20135): 323\u2013333. https:\/\/doi.org\/10.1016\/j.neuropharm.2010.02.009","DOI":"10.1016\/j.neuropharm.2010.02.009"},{"key":"e_1_3_2_28_1","doi-asserted-by":"crossref","unstructured":"Lucas G Rymar VV Sadikot AF et al. (2008) Further evidence for an antidepressant potential of the selective sigma1 agonist SA 4503: Electrophysiological morphological and behavioural studies. International Journal of Neuropsychopharmacology 11(4): 485\u2013495. https:\/\/doi.org\/10.1017\/S1461145708008547","DOI":"10.1017\/S1461145708008547"},{"key":"e_1_3_2_29_1","doi-asserted-by":"crossref","unstructured":"Macfarlane S Grimmer T Teo K et al. (2025) Blarcamesine for the treatment of early Alzheimer\u2019s disease: Results from the ANAVEX2-73-AD-004 phase IIB\/III trial. The Journal of Prevention of Alzheimer\u2019s Disease 12(1): 100016. https:\/\/doi.org\/10.1016\/j.tjpad.2024.100016","DOI":"10.1016\/j.tjpad.2024.100016"},{"key":"e_1_3_2_30_1","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Orozco H Bencomo-Mart\u00ednez A Maya-Arteaga JP et al. (2025) CNEURO-201 an anti-amyloidogenic agent and \u03c31-receptor agonist improves cognition in the 3xtg mouse model of Alzheimer\u2019s disease by multiple actions in the pathology. International Journal of Molecular Sciences 26(3): 1301. https:\/\/doi.org\/10.3390\/ijms26031301","DOI":"10.3390\/ijms26031301"},{"key":"e_1_3_2_31_1","doi-asserted-by":"crossref","unstructured":"Maurice T Lockhart BP Privat A (1996) Amnesia induced in mice by centrally administered \u03b2-amyloid peptides involves cholinergic dysfunction. Brain Research 706(2): 181\u2013193. https:\/\/doi.org\/10.1016\/0006-8993(95)01032-7","DOI":"10.1016\/0006-8993(95)01032-7"},{"key":"e_1_3_2_32_1","doi-asserted-by":"crossref","unstructured":"Maurice T Mustafa MH Desrumaux C et al. (2013) Intranasal formulation of erythropoietin (EPO) showed potent protective activity against amyloid toxicity in the A\u03b225-35 nontransgenic mouse model of Alzheimer\u2019s disease. Journal of Psychopharmacology 27(11): 1044\u20131057. https:\/\/doi.org\/10.1177\/0269881113494939","DOI":"10.1177\/0269881113494939"},{"key":"e_1_3_2_33_1","doi-asserted-by":"crossref","unstructured":"Maurice T Goguadze N (2017) Sigma-1 (\u03c31) Receptor in memory and neurodegenerative diseases. Handbook of Experimental Pharmacology 244: 81\u2013108. https:\/\/doi.org\/10.1007\/164_2017_15","DOI":"10.1007\/164_2017_15"},{"key":"e_1_3_2_34_1","doi-asserted-by":"crossref","unstructured":"Maurice T (2021) Bi-phasic dose response in the preclinical and clinical developments of sigma-1 receptor ligands for the treatment of neurodegenerative disorders. Expert Opinion on Drug Discovery 16(4): 373\u2013389. https:\/\/doi.org\/10.1080\/17460441.2021.1838483","DOI":"10.1080\/17460441.2021.1838483"},{"key":"e_1_3_2_35_1","doi-asserted-by":"crossref","unstructured":"Marrazzo A Caraci F Salinaro ET et al. (2005) Neuroprotective effects of sigma-1 receptor agonists against beta-amyloid-induced toxicity. Neuroreport 16(11): 1223\u20131226. https:\/\/doi.org\/10.1097\/00001756-200508010-00018","DOI":"10.1097\/00001756-200508010-00018"},{"key":"e_1_3_2_36_1","doi-asserted-by":"crossref","unstructured":"Mercer\u00f3n-Mart\u00ednez D Alac\u00e1n Ricardo L Bejerano Pina A et al. (2024) Amylovis-201 enhances physiological memory formation and rescues memory and hippocampal cell loss in a streptozotocin-induced Alzheimer\u2019s disease animal model. Brain Research 1831: 148848. https:\/\/doi.org\/10.1016\/j.brainres.2024.148848","DOI":"10.1016\/j.brainres.2024.148848"},{"key":"e_1_3_2_37_1","doi-asserted-by":"crossref","unstructured":"Meunier J Ieni J Maurice T (2006) The anti-amnesic and neuroprotective effects of donepezil against amyloid beta25-35 peptide-induced toxicity in mice involve an interaction with the sigma1 receptor. British Journal of Clinical Pharmacology 149(8): 998\u20131012. https:\/\/doi.org\/10.1038\/sj.bjp.0706927","DOI":"10.1038\/sj.bjp.0706927"},{"key":"e_1_3_2_38_1","doi-asserted-by":"crossref","unstructured":"Olson AK Eadie BD Ernst C et al. (2006) Environmental enrichment and voluntary exercise massively increase neurogenesis in the adult hippocampus via dissociable pathways. Hippocampus 16(3): 250\u2013260. https:\/\/doi.org\/10.1002\/hipo.20157","DOI":"10.1002\/hipo.20157"},{"key":"e_1_3_2_39_1","volume-title":"The Mouse Brain in Stereotaxic Coordinates","author":"Paxinos G","year":"2004","unstructured":"Paxinos G, Franklin KBJ (2004) The Mouse Brain in Stereotaxic Coordinates, 2nd edn. Elsevier Science.","edition":"2"},{"key":"e_1_3_2_40_1","doi-asserted-by":"crossref","unstructured":"Rivera-Marrero S Bencomo-Mart\u00ednez A Orta Salazar E et al. (2020) A new naphthalene derivative with anti-amyloidogenic activity as potential therapeutic agent for Alzheimer\u2019s disease. Bioorganic & Medicinal Chemistry 28(20): 115700. https:\/\/doi.org\/10.1016\/j.bmc.2020.115700","DOI":"10.1016\/j.bmc.2020.115700"},{"key":"e_1_3_2_41_1","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez Cruz Y Strehaiano M Rodr\u00edguez Obaya T et al. (2017) An intranasal formulation of erythropoietin (Neuro-EPO) prevents memory deficits and amyloid toxicity in the APPSwe transgenic mouse model of Alzheimer\u2019s disease. Journal of Alzheimer\u2019s Disease 55(1): 231\u2013248. https:\/\/doi.org\/10.3233\/JAD-160500","DOI":"10.3233\/JAD-160500"},{"key":"e_1_3_2_42_1","doi-asserted-by":"crossref","unstructured":"Ruscher K Shamloo M Rickhag M et al. (2011) The sigma-1 receptor enhances brain plasticity and functional recovery after experimental stroke. Brain 134(Pt 3): 732\u2013746. https:\/\/doi.org\/10.1093\/brain\/awq367","DOI":"10.1093\/brain\/awq367"},{"key":"e_1_3_2_43_1","doi-asserted-by":"crossref","unstructured":"Selkoe DJ (2013) The therapeutics of Alzheimer\u2019s disease: Where we stand and where we are heading. Annals of Neurology 74(3): 328\u2013336. https:\/\/doi.org\/10.1002\/ana.24001","DOI":"10.1002\/ana.24001"},{"key":"e_1_3_2_44_1","doi-asserted-by":"crossref","unstructured":"Su TP Su TC Nakamura Y et al. (2016) The sigma-1 receptor as a pluripotent modulator in living systems. Trends in Pharmacological Sciences 37(4): 262\u2013278. https:\/\/doi.org\/10.1016\/j.tips.2016.01.003","DOI":"10.1016\/j.tips.2016.01.003"},{"key":"e_1_3_2_45_1","doi-asserted-by":"crossref","unstructured":"Tsai SA Su TP (2017) Sigma-1 receptors fine-tune the neuronal networks. Advances in Experimental Medicine and Biology 964: 79\u201383. https:\/\/doi.org\/10.1007\/978-3-319-50174-1_7","DOI":"10.1007\/978-3-319-50174-1_7"},{"key":"e_1_3_2_46_1","doi-asserted-by":"crossref","unstructured":"Van Praag H Kempermann G Gage FH (2000) Neural consequences of environmental enrichment. Nature Reviews Neuroscience 1(3): 191\u2013198. https:\/\/doi.org\/10.1038\/35044558","DOI":"10.1038\/35044558"},{"key":"e_1_3_2_47_1","doi-asserted-by":"crossref","unstructured":"Vavers E Zvejniece L Maurice T et al. (2019) Allosteric modulators of sigma-1 receptor: A review. Frontiers in Pharmacology 10: 223. https:\/\/doi.org\/10.3389\/fphar.2019.00223","DOI":"10.3389\/fphar.2019.00223"},{"key":"e_1_3_2_48_1","doi-asserted-by":"crossref","unstructured":"Villard V Espallergues J Keller E et al. (2011) Anti-amnesic and neuroprotective potentials of the mixed muscarinic receptor\/sigma1 (\u03c31) ligand ANAVEX2-73 a novel aminotetrahydrofuran derivative. Journal of Psychopharmacology 25(8): 1101\u20131117. https:\/\/doi.org\/10.1177\/0269881110379286","DOI":"10.1177\/0269881110379286"},{"key":"e_1_3_2_49_1","doi-asserted-by":"crossref","unstructured":"Wolf SA Kronenberg G Lehmann K et al. (2006) Cognitive and physical activity differently modulate disease progression in the amyloid precursor protein (APP)-23 model of Alzheimer\u2019s disease. Biological Psychiatry 60(12): 1314\u20131323. https:\/\/doi.org\/10.1016\/j.biopsych.2006.04.004","DOI":"10.1016\/j.biopsych.2006.04.004"},{"key":"e_1_3_2_50_1","doi-asserted-by":"crossref","unstructured":"Young D Lawlor PA Leone P et al. (1999) Environmental enrichment inhibits spontaneous apoptosis prevents seizures and is neuroprotective. Nature Medicine 5(4): 448\u2013453. https:\/\/doi.org\/10.1038\/7449","DOI":"10.1038\/7449"},{"key":"e_1_3_2_51_1","doi-asserted-by":"crossref","unstructured":"Zussy C Brureau A Keller E et al. (2013) Alzheimer\u2019s disease related markers cellular toxicity and behavioral deficits induced six weeks after oligomeric amyloid-\u03b2 peptide injection in rats. PLoS One 8(1): e53117. https:\/\/doi.org\/10.1371\/journal.pone.0053117","DOI":"10.1371\/journal.pone.0053117"}],"container-title":["Journal of Psychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/02698811261458343","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/02698811261458343","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/02698811261458343","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T12:58:09Z","timestamp":1782478689000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/02698811261458343"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,24]]},"references-count":50,"alternative-id":["10.1177\/02698811261458343"],"URL":"https:\/\/doi.org\/10.1177\/02698811261458343","relation":{},"ISSN":["0269-8811","1461-7285"],"issn-type":[{"value":"0269-8811","type":"print"},{"value":"1461-7285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,24]]},"article-number":"02698811261458343"}}