Inflammatory Microglia Disrupt the Cholinergic Systems of the Aging Brain
Cholinergic neurons are important in many functions in the brain. It is becoming apparent that chronic inflammation in brain tissue is an important contributing cause in the decline of cholinergic systems of brain function. Microglia, innate immune cells of the brain, are one of the cell populations responsible for sustaining harmful inflammation. These cells become active and inflammatory in ever increasing numbers in the aging brain, a maladaptive reaction to growing levels of metabolic waste and pro-inflammatory signaling outside cells, alongside age-related dysfunction inside cells.
This study assessed the effect of normal aging and neuroinflammation on the medial septal Iba-1+ microglia population and the consequential effect on the choline acetyl transferase (ChAT)+ cholinergic cell population. Chronic IL-6 expression in the mouse brain significantly increased the reactive Iba-1+ microglia and decreased the ChAT+ cholinergic cell number in the medial septum and this tendency exacerbated with aging. We also showed that aging and chronic IL-6 expression reorientated the septal microglia morphology towards a more reactive and de-ramified pro-inflammatory phenotype.
These findings further reflected upon the septal cholinergic cell population displaying a neurodegenerative phenotype. The resultant direct effect of neuroinflammation and aging on the septal cholinergic population mirrored upon the hippocampal pyramidal cell dendritic spine density. Overall, these findings demonstrate a potential detrimental effect of chronic microglia activation on the medial septum, which can exacerbate throughout aging, leading to cholinergic dysfunction that could in turn disrupt hippocampal pyramidal cell network regulation.