Chronic glial activation causes cholinergic cell loss in the basal forebrain during pathological aging

Background Neuroinflammation, described by chronic glial reactivation lead to gradual neurodegeneration during pathological aging, contributing disorders like Alzheimer’s disease (AD). Cholinergic cell loss in the basal forebrain (BF) including medial septum (MS) is associated with AD; however underlying mechanism still unknown. Hence, this study investigated effects of aging and neuroinflammation on MS cholinergic numbers morphology. Method Aged, 12 24 months WT GFAP-IL6 mice (presenting IL-6 overexpression under GFAP promoter, resulting activation) were used. Immunohistochemistry combined unbiased stereology 3D morphology analysis used estimate number Iba1+ microglia ChAT+ cells MS. Transcriptomic was performed using qPCR. Result Stereological estimation displayed a significant 25% increase compared control (12M). A 30% obtained for (24M) (24M). Furthermore, 23% (12M) mice. 28% 38% decrease microglial surface area, volume respectively observed between GFAP-IL mice, as well 26% 34% (24M), resembling reactive Meanwhile, 31% While There tendency ageing among cohorts. 58% 67% reduction dendritic field 41% 46% displaying patterns neuronal degeneration. Conclusion These findings demonstrate impact both activation alone MS, AD, which can exacerbate throughout leading neurodegenerative impairments.