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Many aspects of GABAergic neurotransmission, including the densities of GABAergic neurons, the synthesis of GABA and its interaction with the respective receptors, are believed to be altered during aging, contributing to increased neuronal excitability seen in multiple neurodegenerative conditions, such as dementias, Alzheimer's disease, and traumatic brain injury (TBI). Oral administration of a nuclear fraction extract of the bovine thymus gland (thymus nuclear fraction\u2014TNF) to rats was recently reported to improve their functional recovery from controlled cortical impact (CCI)\u2014an animal model of TBI. Given that individual thymic peptides and mixed thymus fractions were also found to have broad neuroprotective effects and anti\u2010neuroinflammatory activity, we sought to investigate the impact of TNF on GABAergic neurotransmission in the aging mouse brain. Using biochemical investigation, electrophysiological recordings, obtained using electroencephalography (EEG), and power spectral density analysis, we evaluated GABAergic protein expression and cortical neuronal activity in aged control mice and in mice supplemented with a low dose (LD) or a high dose of TNF for 14\u2009weeks. We uncovered increased expression of two isoforms of glutamic acid decarboxylase, GAD65 and GAD67, and increased levels of \u03b22\/\u03b23 subunits of GABA\n                    <jats:sub>A<\/jats:sub>\n                    receptor in the brains of TNF\u2010supplemented mice compared to the control group, suggesting possible enhancement of inhibitory neurotransmission. Decreased neuronal excitability, evidenced by reduced EEG amplitudes, power spectral densities, and peak amplitudes of high\u2010frequency cortical oscillations, further confirmed a dose\u2010dependent attenuation of neuronal excitability by TNF. Our results suggest that TNF supplementation may have the potential to mitigate age\u2010related alterations in GABAergic neurotransmission, thereby modulating neuronal excitability.\n                  <\/jats:p>","DOI":"10.1096\/fba.2025-00256","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T15:00:21Z","timestamp":1769785221000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Oral Supplementation With a Bovine Thymus Extract Reduces Neuronal Excitability in Aging Mice"],"prefix":"10.1096","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3610-7259","authenticated-orcid":false,"given":"Abdeslem","family":"El\u2010Idrissi","sequence":"first","affiliation":[{"name":"Department of Biology and Center for Developmental Neuroscience, College of Staten Island The City University of New York  New York New York USA"},{"name":"Biology Program, The Graduate Center The City University of New York  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5816-7425","authenticated-orcid":false,"given":"Natalia","family":"Surzenko","sequence":"additional","affiliation":[{"name":"Nutrition Innovation Center Standard Process Inc  Kannapolis North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3509-1753","authenticated-orcid":false,"given":"Bassem F.","family":"El\u2010Khodor","sequence":"additional","affiliation":[{"name":"Nutrition Innovation Center Standard Process Inc  Kannapolis North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23115938"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12993-021-00179-9"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2021.111575"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1515\/revneuro-2018-0096"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24152678"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6655064"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858411422114"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-018-0214-6"},{"key":"e_1_2_9_10_1","article-title":"Developmental Changes in GABAergic Mechanisms in Human Visual Cortex Across the Lifespan","volume":"4","author":"Pinto J. 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