{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:14:25Z","timestamp":1779927265764,"version":"3.53.1"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T00:00:00Z","timestamp":1744848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive and non-cognitive decline associated with neuropathological hallmarks, including neuroinflammation. Palmitoylethanolamide (PEA), an endogenous lipid with anti-inflammatory and neuroprotective properties, has emerged as a promising therapeutic agent in managing AD. This study investigated the therapeutic effects of chronic (6-months) PEA administration <jats:italic>via<\/jats:italic> subcutaneous pellet in Tg2576 mice, a validated model of AD. The impact of PEA on amyloid precursor protein (APP) processing, astrocytic activation, microglial reactivity and neuroinflammation, nitrosative stress, dendritic spine density in hippocampal CA1 pyramidal neurons, and cognitive performance was assessed. Chronic PEA treatment of Tg2576 mice increased the expression of the \u03b1-secretase ADAM9 and reduced astrogliosis. Furthermore, PEA attenuated microglia reactivity, downregulated pro-inflammatory (CXCL13, MCP-1, GCSF) and upregulated anti-inflammatory (CXC3CL1 and IL-9) cytokine expression. Chronic PEA administration also decreased protein nitrosylation, downregulated calcineurin expression, restored dendritic spine density, and improved cognitive functions. Chronic PEA administration offers a promising therapeutic approach for AD by mitigating neuroinflammation, oxidative stress, and synaptic dysfunction, ultimately leading to cognitive function restoration.<\/jats:p>","DOI":"10.3389\/fncel.2025.1571428","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T05:24:05Z","timestamp":1744867445000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Chronic palmitoylethanolamide administration via slow-release subcutaneous pellets promotes neuroprotection and mitigates neuroinflammation in the Tg2576 mouse model of Alzheimer\u2019s disease"],"prefix":"10.3389","volume":"19","author":[{"given":"Daniel","family":"Tortolani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Decandia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Giacovazzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Scipioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Panuccio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ciaramellano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Eugelio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Fanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele Claudio","family":"Latagliata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"La Barbera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Cutuli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Compagnone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"D\u2019Amelio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Coccurello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Oddi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Petrosini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Maccarrone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.bbr.2007.03.001","article-title":"A natural scavenger of peroxynitrites, rosmarinic acid, protects against impairment of memory induced by Abeta (25-35)","volume":"180","author":"Alkam","year":"2007","journal-title":"Behav. Brain Res."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e17397","DOI":"10.1371\/journal.pone.0017397","article-title":"DHA improves cognition and prevents dysfunction of entorhinal cortex neurons in 3xTg-AD mice","volume":"6","author":"Arsenault","year":"2011","journal-title":"PLoS One"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1016\/s0006-291x(02)02999-6","article-title":"Putative function of ADAM9, ADAM10, and ADAM17 as APP alpha-secretase","volume":"301","author":"Asai","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1152\/jn.00278.2019","article-title":"Object and place information processing by CA1 hippocampal neurons of C57BL\/6J mice","volume":"123","author":"\u00c1sgeirsd\u00f3ttir","year":"2020","journal-title":"J. Neurophysiol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"7205747","DOI":"10.1155\/2016\/7205747","article-title":"Nitric oxide: exploring the contextual link with Alzheimer\u2019s disease","volume":"2016","author":"Asiimwe","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"821","DOI":"10.3389\/fphar.2019.00821","article-title":"Palmitoylethanolamide (PEA) as a potential therapeutic agent in Alzheimer\u2019s disease","volume":"10","author":"Beggiato","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"890855","DOI":"10.3389\/fnagi.2022.890855","article-title":"Effects of Ultramicronized Palmitoylethanolamide on mitochondrial bioenergetics, cerebral metabolism, and glutamatergic transmission: an integrated approach in a triple transgenic mouse model of Alzheimer\u2019s disease","volume":"14","author":"Bellanti","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref8","author":"Bengtsson","year":"2024"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"8230","DOI":"10.3390\/ijms24098230","article-title":"CX3CL1 pathway as a molecular target for treatment strategies in Alzheimer\u2019s disease","volume":"24","author":"Bivona","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"101","DOI":"10.3390\/brainsci12010101","article-title":"Is it time to test the Antiseizure potential of Palmitoylethanolamide in human studies? A systematic review of preclinical evidence","volume":"12","author":"Bortoletto","year":"2022","journal-title":"Brain Sci."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.3390\/brainsci13081138","article-title":"Effects of long-term Oral administration of N-Palmitoylethanolamine in subjects with mild cognitive impairment: study protocol","volume":"13","author":"Bossa","year":"2023","journal-title":"Brain Sci."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"818","DOI":"10.3390\/antiox9090818","article-title":"Mitochondrial oxidative and Nitrosative stress and Alzheimer disease","volume":"9","author":"Butterfield","year":"2020","journal-title":"Antioxidants"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"856376","DOI":"10.3389\/fimmu.2022.856376","article-title":"Microglia in the neuroinflammatory pathogenesis of Alzheimer\u2019s disease and related therapeutic targets","volume":"13","author":"Cai","year":"2022","journal-title":"Front. Immunol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1007\/s12017-013-8241-2","article-title":"Calcineurin inhibition rescues early synaptic plasticity deficits in a mouse model of Alzheimer\u2019s disease","volume":"15","author":"Cavallucci","year":"2013","journal-title":"NeuroMolecular Med."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1186\/s12974-023-02853-3","article-title":"Tau and neuroinflammation in Alzheimer\u2019s disease: interplay mechanisms and clinical translation","volume":"20","author":"Chen","year":"2023","journal-title":"J. Neuroinflammation"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"7790","DOI":"10.3390\/ijms21207790","article-title":"An overview of ADAM9: structure, activation, and regulation in human diseases","volume":"21","author":"Chou","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"854560","DOI":"10.1155\/2014\/854560","article-title":"Short-term efficacy of ultramicronized palmitoylethanolamide in peripheral neuropathic pain","volume":"2014","author":"Cocito","year":"2014","journal-title":"Pain Res. Treat."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.bbr.2014.08.002","article-title":"Assessing rodent hippocampal involvement in the novel object recognition task. A review","volume":"285","author":"Cohen","year":"2015","journal-title":"Behav. Brain Res."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1784","DOI":"10.1038\/npp.2012.25","article-title":"Palmitoylethanolamide protects against the amyloid-\u03b225-35-induced learning and memory impairment in mice, an experimental model of Alzheimer disease","volume":"37","author":"D\u2019Agostino","year":"2012","journal-title":"Neuropsychopharmacology"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"3054","DOI":"10.3390\/ijms22063054","article-title":"Palmitoylethanolamide modulation of microglia activation: characterization of mechanisms of action and implication for its neuroprotective effects","volume":"22","author":"D\u2019Aloia","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/nn.2709","article-title":"Caspase-3 triggers early synaptic dysfunction in a mouse model of Alzheimer\u2019s disease","volume":"14","author":"D\u2019Amelio","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1152\/physrev.00039.2016","article-title":"Neuroimmune interactions: from the brain to the immune system and vice versa","volume":"98","author":"Dantzer","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.pbb.2006.08.007","article-title":"Beneficial effects of galantamine on performance in the object recognition task in Swiss mice: deficits induced by scopolamine and by prolonging the retention interval","volume":"85","author":"de Bruin","year":"2006","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00401-015-1449-5","article-title":"Analyzing dendritic spine pathology in Alzheimer\u2019s disease: problems and opportunities","volume":"130","author":"Dorostkar","year":"2015","journal-title":"Acta Neuropathol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"124392","DOI":"10.1016\/j.talanta.2023.124392","article-title":"Determination of endocannabinoids and their conjugated congeners in the brain by means of \u03bcSPE combined with UHPLC-MS\/MS","volume":"257","author":"Fanti","year":"2023","journal-title":"Talanta"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s12974-019-1412-9","article-title":"Neuroinflammation and fractalkine signaling in Alzheimer\u2019s disease","volume":"16","author":"Finneran","year":"2019","journal-title":"J. Neuroinflammation"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"747","DOI":"10.2147\/DDDT.S48324","article-title":"N-Palmitoylethanolamine depot injection increased its tissue levels and those of other acylethanolamide lipids","volume":"7","author":"Grillo","year":"2013","journal-title":"Drug Des. Devel. Ther."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1186\/s12974-024-03120-9","article-title":"Interleukin-9 protects from microglia- and TNF-mediated synaptotoxicity in experimental multiple sclerosis","volume":"21","author":"Guadalupi","year":"2024","journal-title":"J. Neuroinflammation"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"38","DOI":"10.4103\/0975-7406.124315","article-title":"Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs","volume":"6","author":"Guarnieri","year":"2014","journal-title":"J. Pharm. Bioallied Sci."},{"key":"ref30","volume-title":"Ggplot2: elegrant graphics for data analysis","author":"Hadley","year":"2016"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1442","DOI":"10.1093\/cercor\/bhr229","article-title":"Evidence that microglia mediate the neurobiological effects of chronic psychological stress on the medial prefrontal cortex","volume":"22","author":"Hinwood","year":"2012","journal-title":"Cereb. Cortex"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1784","DOI":"10.1093\/cercor\/bhs151","article-title":"Chronic stress induced remodeling of the prefrontal cortex: structural re-organization of microglia and the inhibitory effect of minocycline","volume":"23","author":"Hinwood","year":"2013","journal-title":"Cereb. Cortex"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.semcdb.2019.02.005","article-title":"Rod microglia and their role in neurological diseases","volume":"94","author":"Holloway","year":"2019","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/s0531-5565(98)00045-x","article-title":"Transgenic mice expressing Alzheimer amyloid precursor proteins","volume":"33","author":"Hsiao","year":"1998","journal-title":"Exp. Gerontol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1186\/s12974-014-0136-0","article-title":"Micronized\/ultramicronized palmitoylethanolamide displays superior oral efficacy compared to nonmicronized palmitoylethanolamide in a rat model of inflammatory pain","volume":"11","author":"Impellizzeri","year":"2014","journal-title":"J. Neuroinflammation"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"2651","DOI":"10.1016\/j.immuni.2024.09.014","article-title":"Apolipoprotein E aggregation in microglia initiates Alzheimer's disease pathology by seeding \u03b2-amyloidosis","volume":"57","author":"Kaji","year":"2024","journal-title":"Immunity"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1186\/s12974-022-02532-9","article-title":"Repopulated microglia induce expression of Cxcl13 with differential changes in tau phosphorylation but do not impact amyloid pathology","volume":"19","author":"Karaahmet","year":"2022","journal-title":"J. Neuroinflammation"},{"key":"ref38","author":"Kassambara","year":"2023"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"3945","DOI":"10.1038\/s41467-019-11928-w","article-title":"Blunting neuroinflammation with resolvin D1 prevents early pathology in a rat model of Parkinson\u2019s disease","volume":"10","author":"Krashia","year":"2019","journal-title":"Nat. Commun."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1111\/jnc.15565","article-title":"Reactive astrogliosis: a friend or foe in the pathogenesis of Alzheimer\u2019s disease","volume":"164","author":"Kumar","year":"2023","journal-title":"J. Neurochem."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"667","DOI":"10.3390\/biom12050667","article-title":"Effects of palmitoylethanolamide on neurodegenerative diseases: a review from rodents to humans","volume":"12","author":"Landolfo","year":"2022","journal-title":"Biomol. Ther."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","article-title":"Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?","volume":"17","author":"Leng","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"1142739","DOI":"10.3389\/fneur.2023.1142739","article-title":"Prolonged exposure of neonatal mice to sevoflurane leads to hyper-ramification in microglia, reduced contacts between microglia and synapses, and defects in adult behavior","volume":"14","author":"Li","year":"2023","journal-title":"Front. Neurol."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1016\/j.phrs.2018.02.009","article-title":"Early alteration of distribution and activity of hippocampal type-1 cannabinoid receptor in Alzheimer\u2019s disease-like mice overexpressing the human mutant amyloid precursor protein","volume":"130","author":"Maccarrone","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1281882","DOI":"10.3389\/fimmu.2023.1281882","article-title":"Targeting CaN\/NFAT in Alzheimer\u2019s brain degeneration","volume":"14","author":"Mackiewicz","year":"2023","journal-title":"Front. Immunol."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"102575","DOI":"10.1016\/j.conb.2022.102575","article-title":"How neurons die in Alzheimer\u2019s disease: implications for neuroinflammation","volume":"75","author":"Mangalmurti","year":"2022","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1111\/jnc.13411","article-title":"The contribution of neuroinflammation to amyloid toxicity in Alzheimer\u2019s disease","volume":"136","author":"Minter","year":"2016","journal-title":"J. Neurochem."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"14727","DOI":"10.1038\/ncomms14727","article-title":"Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer\u2019s disease","volume":"8","author":"Nobili","year":"2017","journal-title":"Nat. Commun."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1152\/physrev.00029.2006","article-title":"Nitric oxide and peroxynitrite in health and disease","volume":"87","author":"Pacher","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref50","volume-title":"Paxinos and Franklin\u2019s the mouse brain in stereotaxic coordinates, 5th Edition. San Diego: Elsevier Academic Press","author":"Paxinos","year":"2019"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"1900015","DOI":"10.1002\/ejlt.201900015","article-title":"Targeted Lipidomics investigation of N-acylethanolamines in a transgenic mouse model of AD: a longitudinal study","volume":"121","author":"Piscitelli","year":"2019","journal-title":"Eur. J. Lipid Sci. Technol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"359","DOI":"10.31083\/j.jin.2020.02.110","article-title":"Genetic factors related to the immune system in subjects at risk of developing Alzheimer\u2019s disease","volume":"19","author":"Prendecki","year":"2020","journal-title":"J. Integr. Neurosci."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"7942","DOI":"10.3390\/ijms21217942","article-title":"The basal pharmacology of palmitoylethanolamide","volume":"21","author":"Rankin","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"685","DOI":"10.2174\/157015911798376316","article-title":"A role for calcineurin in Alzheimer\u2019s disease","volume":"9","author":"Reese","year":"2011","journal-title":"Curr. Neuropharmacol."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/j.celrep.2013.07.028","article-title":"Regulation of cyclic AMP response element binding and hippocampal plasticity-related genes by peroxisome proliferator-activated receptor \u03b1","volume":"4","author":"Roy","year":"2013","journal-title":"Cell Rep."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.cmet.2015.05.022","article-title":"HMG-CoA reductase inhibitors bind to PPAR\u03b1 to upregulate neurotrophin expression in the brain and improve memory in mice","volume":"22","author":"Roy","year":"2015","journal-title":"Cell Metab."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1007\/s11481-014-9582-9","article-title":"PPAR\u03b1 signaling in the hippocampus: crosstalk between fat and memory","volume":"10","author":"Roy","year":"2015","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"6684","DOI":"10.3390\/ijms24076684","article-title":"A\u03b2 chronic exposure promotes an activation state of microglia through endocannabinoid signalling imbalance","volume":"24","author":"Scipioni","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1038\/s41398-017-0076-4","article-title":"Ultramicronized palmitoylethanolamide rescues learning and memory impairments in a triple transgenic mouse model of Alzheimer\u2019s disease by exerting anti-inflammatory and neuroprotective effects","volume":"8","author":"Scuderi","year":"2018","journal-title":"Transl. Psychiatry"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"2664","DOI":"10.1111\/j.1582-4934.2011.01267.x","article-title":"Palmitoylethanolamide counteracts reactive astrogliosis induced by \u03b2-amyloid peptide","volume":"15","author":"Scuderi","year":"2011","journal-title":"J. Cell. Mol. Med."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"e1419","DOI":"10.1038\/cddis.2014.376","article-title":"Palmitoylethanolamide controls reactive gliosis and exerts neuroprotective functions in a rat model of Alzheimer\u2019s disease","volume":"5","author":"Scuderi","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/s12974-022-02565-0","article-title":"Astrocytic and microglial cells as the modulators of neuroinflammation in Alzheimer\u2019s disease","volume":"19","author":"Singh","year":"2022","journal-title":"J. Neuroinflammation"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1016\/j.bbi.2019.05.042","article-title":"Microglial cell hyper-ramification and neuronal dendritic spine loss in the hippocampus and medial prefrontal cortex in a mouse model of PTSD","volume":"80","author":"Smith","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"20966","DOI":"10.1073\/pnas.0907417106","article-title":"Selective N-acylethanolamine-hydrolyzing acid amidase inhibition reveals a key role for endogenous palmitoylethanolamide in inflammation","volume":"106","author":"Solorzano","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"2780","DOI":"10.3390\/ijms22052780","article-title":"Microglial heterogeneity and its potential role in driving phenotypic diversity of Alzheimer\u2019s disease","volume":"22","author":"Sorrentino","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"3758","DOI":"10.1038\/s41467-019-11674-z","article-title":"Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer's disease model","volume":"10","author":"Spangenberg","year":"2019","journal-title":"Nat. Commun."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"113969","DOI":"10.1016\/j.expneurol.2021.113969","article-title":"Early derailment of firing properties in CA1 pyramidal cells of the ventral hippocampus in an Alzheimer\u2019s disease mouse model","volume":"350","author":"Spoleti","year":"2022","journal-title":"Exp. Neurol."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.nlm.2016.06.016","article-title":"Temporary inactivation reveals that the CA1 region of the mouse dorsal hippocampus plays an equivalent role in the retrieval of long-term object memory and spatial memory","volume":"133","author":"Stackman","year":"2016","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"2021","DOI":"10.1089\/ars.2006.8.2021","article-title":"Protein oxidation and lipid peroxidation in brain of subjects with Alzheimer\u2019s disease: insights into mechanism of neurodegeneration from redox proteomics","volume":"8","author":"Sultana","year":"2006","journal-title":"Antioxid. Redox Signal."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10753-022-01721-1","article-title":"Neuroinflammation in Alzheimer\u2019s disease: current Progress in molecular signaling and therapeutics","volume":"46","author":"Thakur","year":"2023","journal-title":"Inflammation"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"6518","DOI":"10.3390\/ijms24076518","article-title":"Inflammatory processes in Alzheimer\u2019s disease-pathomechanism, diagnosis and treatment: a review","volume":"24","author":"Twarowski","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s00429-012-0493-3","article-title":"Cytoarchitecture of mouse and rat cingulate cortex with human homologies","volume":"219","author":"Vogt","year":"2014","journal-title":"Brain Struct. Funct."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bbi.2013.12.010","article-title":"Dynamic structural remodelling of microglia in health and disease: a review of the models, the signals and the mechanisms","volume":"37","author":"Walker","year":"2014","journal-title":"Brain Behav. Immun."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"27131","DOI":"10.1038\/srep27131","article-title":"Altered resting-state functional activity in posttraumatic stress disorder: a quantitative meta-analysis","volume":"6","author":"Wang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref75","volume-title":"dplyr: a grammar of data manipulation","author":"Wickham","year":"2020"}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2025.1571428\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T05:24:11Z","timestamp":1744867451000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2025.1571428\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,17]]},"references-count":75,"alternative-id":["10.3389\/fncel.2025.1571428"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2025.1571428","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,17]]},"article-number":"1571428"}}