{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T18:25:05Z","timestamp":1794507905853,"version":"4.9.1"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T00:00:00Z","timestamp":1700697600000},"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. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Neuroinflammation is a common feature of many psychiatric disorders as well as a common underlying mechanism of neurodegenerative diseases. Sex has been shown to strongly influence the development as well as the clinical expression of these pathologies. However, there is still a neglect regarding the consideration of sex effects in rodent experiments, and a substantial underrepresentation of females in studies. This work set out to expand our knowledge of neuroinflammatory mechanisms in female mice, at both a behavioral and molecular level.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study used GFAP-IL6 mice, a model of chronic neuroinflammation, in which interleukin-6 (IL6) is overexpressed in the central nervous system under the control of the glial fibrillary acidic protein (GFAP) promoter. We evaluated aged (11-15-month-old) wild type-like (WT) and GFAP-IL6 female mice in behavioral tests assessing anxiety (elevated plus-maze, EPM, Light\/dark box), and spatial learning and memory (Y-maze, YM and Barnes Maze, BM) and associative learning (fear conditioning, FC). We also examined gene expression of markers linked to neuroinflammation, neurodegeneration and neurotransmission via RT-qPCR in brain regions involved in motor control, anxiety, learning and memory.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Female GFAP-IL6 mice exhibited reduced anxiety-like behavior in the EPM, and hypolocomotion in the light-dark test and EPM. Short-term memory impairment was evident in the YM but associative learning in FC was intact in GFAP-IL6 mice, suggesting domain-specific cognitive deficits in female GFAP-IL6 mice. In the BM, all mice showed intact learning and memory, but GFAP-IL6 mice exhibited higher latencies to enter the escape hole than WT mice. We analyzed the search strategy and found differences in the way GFAP-IL6 mice searched for the escape hole compared to WTs. RT-qPCR showed increased mRNA levels for molecules involved in pro-inflammatory pathways in the cerebellum, motor cortex, hippocampus, and amygdala in GFAP-IL6 mice. Of the regions examined, the cerebellum and the hippocampus showed upregulation of neuroinflammatory makers as well as dysregulation of glutamatergic and GABAergic neurotransmission gene expression in GFAP-IL6 mice compared to WTs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In conclusion, we showed that chronic neuroinflammation via IL6 overexpression in aged female mice led to a less anxious-like phenotype, hypolocomotion and impaired intermediate-term spatial learning and memory in the YM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2023.1267818","type":"journal-article","created":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T11:33:24Z","timestamp":1700739204000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Chronic interleukin-6 mediated neuroinflammation decreases anxiety, and impaires spatial memory in aged female mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Ingrid Marguerite","family":"Wagnon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lillian Jocelyn","family":"Jabur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garry","family":"Niedermayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald","family":"M\u00fcnch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Karl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose","family":"Chesworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Gyengesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"417","DOI":"10.3109\/09540261.2010.515205","article-title":"Sex differences in schizophrenia","volume":"22","author":"Abel","year":"2010","journal-title":"Int. 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