{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T06:31:20Z","timestamp":1773210680954,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["25K01969"],"award-info":[{"award-number":["25K01969"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gamma-aminobutyric acid (GABA) has been implicated in gut\u2013brain interactions and neuronal activation. We hypothesized that GABA could ameliorate memory decline. We investigated whether oral GABA administration ameliorated age-related cognitive decline in aged mice (C57BL\/6J, male) and explored the role of circulating exosomes in mediating these effects. Aged mice that drank water containing 0.5% GABA exhibited significantly improved discrimination index scores compared with that of controls, indicating enhanced memory function. Their plasma-derived exosomes induced neurite outgrowth and mitochondrial activation and restored neuronal activity in SH-SY5Y cells. GABA enhanced the exosomal expression of several miRNAs linked to neuronal activation, longevity, and anti-senescence pathways. Plasma-derived exosomes also restored object recognition memory, reduced hippocampal neuroinflammation, and decreased senescent cell markers (p21 and \u03b3H2AX) in aged mice. Additionally, mitochondria- and neurite-related genes were upregulated, and pathways associated with oxidative phosphorylation and Alzheimer\u2019s disease were enriched. Collectively, long-term GABA administration was found to improve cognitive function of aged mice through the secretion of functional exosomes.<\/jats:p>","DOI":"10.3390\/ijms27062519","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T08:43:31Z","timestamp":1773132211000},"page":"2519","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["GABA-Induced Exosomes Improve Memory Impairment in Aged Mice"],"prefix":"10.3390","volume":"27","author":[{"given":"Yukina","family":"Akama","sequence":"first","affiliation":[{"name":"Graduate School of Bioresources and Bioenvironmental Sciences, Kyushu University, Fukuoka 819-0395, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunsuke","family":"Maeda","sequence":"additional","affiliation":[{"name":"Graduate School of Bioresources and Bioenvironmental Sciences, Kyushu University, Fukuoka 819-0395, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miyako","family":"Udono","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9487-0522","authenticated-orcid":false,"given":"Utano","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Pharma Foods International Co., Ltd., Kyoto 615-8245, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6384-3193","authenticated-orcid":false,"given":"Yusuke","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Pharma Foods International Co., Ltd., Kyoto 615-8245, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youngil","family":"Kim","sequence":"additional","affiliation":[{"name":"Pharma Foods International Co., Ltd., Kyoto 615-8245, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4237-5081","authenticated-orcid":false,"given":"Bungo","family":"Shirouchi","sequence":"additional","affiliation":[{"name":"Faculty of Nursing and Nutrition, University of Nagasaki, Nagasaki 851-2195, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiichiro","family":"Teruya","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9678-9602","authenticated-orcid":false,"given":"Yoshinori","family":"Katakura","sequence":"additional","affiliation":[{"name":"Faculty of Agriculture, Kyushu University, Fukuoka 819-0395, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1016\/j.cmet.2018.05.011","article-title":"Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States","volume":"27","author":"Mattson","year":"2018","journal-title":"Cell Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/nrn3200","article-title":"The ageing cortical synapse: Hallmarks and implications for cognitive decline","volume":"13","author":"Morrison","year":"2012","journal-title":"Nat. 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