The impact of aging and neuroinflammation on the mouse brain and the anti-inflammatory effects of apigenin and curcumin

Abstract

The current project investigated the susceptibility of specific rodent brain regions, such as the medial septum (MS) of the basal forebrain (BF), hippocampus, and cerebellum, to aging and neuroinflammation using the GFAP-IL6 (brain specific overexpression of astroglial IL-6 under the control of GFAP promoter) transgenic mouse model of chronic low-grade neuroinflammation. Advanced histology, stereology microscopy, and 3D morphology analysis were employed to examine the impact of aging and neuroinflammation on microglia and neurons. Chapter 1: Reviews the role of resident immune cells (microglia and astrocytes) of the CNS in normal aging and pathological aging, while elucidating their role in maintaining BFCN homeostasis, and the reciprocal contribution of the cholinergic system to maintain glial homeostasis. Chapter 2: Reviews the morphological characteristics of microglia and astrocytes under normal physiological state and in neuroinflammation, as well as the effect of anti-inflammatory agents such as curcumin on their activation state. Chapter 3: Investigated the reliability of the ChATBAC-eGFP mouse model to study the cholinergic system in the mouse brain, with special consideration on the BF cholinergic cell population. Also, highlighting occasional discrepancies between labeling with eGFP and antibodies to cholinergic neuronal marker, choline acetyltransferase (ChAT). Chapter 4: Investigated the impact of chronic microglial activation on the BF-MS cholinergic system and hippocampal pyramidal spine density. Chapter 5: Investigated whether chronic treatment with the natural flavonoid, apigenin, could reduce microglia activation in the hippocampus and improve spatial memory. Chapter 6: Investigated the effect of microglial activation and aging on the total number of cerebellar Purkinje cells and the morphology of their dendritic arborization. Overall, a significant impact of both aging and neuroinflammation was observed in all the three brain regions, resulting in changes in the number and morphology of microglia and neurons, ultimately leading to cognitive and motor dysfunctions. Moreover, anti-inflammatory agents such as curcumin could be therapeutically favourable in reversing gliosis and associated neurodegeneration. However, it is inconclusive that inflammation is a cause or a result of the observed neurodegeneration in neurodegenerative diseases like AD. Thus, advanced studies equally focussing on both neuroinflammation and neurodegeneration will help to design target specific therapeutic interventions when treating AD or other related cognitive impairments.

Date of Award	2023
Original language	English