Chronic interleukin-6 mediated neuroinflammation decreases anxiety, and impaires spatial memory in aged female mice

• DOI: 10.3389/fnins.2023.1267818
• Publication Date: 2023-11-23T16:33:24Z
• Authors: Ingrid Marguerite...; Lillian Jocelyn J...; Garry Niedermayer; Gerald Münch; Tim Karl; Rose Chesworth; Erika Gyengesi
• Keywords: Barnes maze; Elevated plus maze; Rotarod performance test

Neuroinflammation is a common feature of many psychiatric disorders as well underlying mechanism neurodegenerative diseases. Sex has been shown to strongly influence the development clinical expression these pathologies. However, there still neglect regarding consideration sex effects in rodent experiments, and substantial underrepresentation females studies. This work set out expand our knowledge neuroinflammatory mechanisms female mice, at both behavioral molecular level.This study used GFAP-IL6 model chronic neuroinflammation, which interleukin-6 (IL6) overexpressed central nervous system under control glial fibrillary acidic protein (GFAP) promoter. We evaluated aged (11-15-month-old) wild type-like (WT) mice tests assessing anxiety (elevated plus-maze, EPM, Light/dark box), spatial learning memory (Y-maze, YM Barnes Maze, BM) associative (fear conditioning, FC). also examined gene markers linked neurodegeneration neurotransmission via RT-qPCR brain regions involved motor control, anxiety, memory.Female exhibited reduced anxiety-like behavior hypolocomotion light-dark test EPM. Short-term impairment was evident but FC intact suggesting domain-specific cognitive deficits mice. In BM, all showed memory, higher latencies enter escape hole than WT analyzed search strategy found differences way searched for compared WTs. increased mRNA levels molecules pro-inflammatory pathways cerebellum, cortex, hippocampus, amygdala Of examined, cerebellum hippocampus upregulation makers dysregulation glutamatergic GABAergic WTs.In conclusion, we that neuroinflammation IL6 overexpression led less anxious-like phenotype, impaired intermediate-term YM.