Microglial Phagocytosis in Rats With Different Models of Alzheimer's Disease

Abstract

Neuroinflammation is a key feature of Alzheimer's disease (AD), a progressive neurodegenerative disorder. Microglia, the resident immune cells of the central nervous system, play a crucial role in the pathogenesis of AD and are active participants in neuroinflammation. Adequate reproduction of neuroinflammation in animal models is one of the main methodological approaches for studying AD pathogenesis and pathophysiology. The aim of the study was to conduct a comparative assessment of the phagocytic activity of microglia in rats with AD induced by intrahippocampal administration of beta-amyloid (Aβ) 1-40 and Aβ25-35. Materials and methods. Wistar male rats were used in the study. Intact and sham-operated animals were used as controls. The development of the disease was confirmed by the assessment of cognitive impairment in the Barnes maze behavioral test, as well as by the level of dopaminergic neurons (DN). The phagocytic activity of microglia, as well as oxidative metabolism and the expression of phenotypic markers CD80 and CD206 were determined by flow cytometry. Results. In animals with Aβ 1-40-induced AD, significant impairment of cognitive activity and loss of DN were registered, microglial cells were characterized by an increase in the proportion of phagocytic cells and an increase in their endocytic activity, augmented oxidative metabolism and overexpression of CD86 and CD206. In animals with Aβ 25-35-induced AD, moderate impairment of cognitive activity was observed, microglial cells were characterized only by an increase in the number of phagocytizing cells without changes in their endocytic activity, oxidative metabolism, and expression of phenotypic markers. Conclusion. Thus, in animals with Aβ1–40-induced AD, the pro-inflammatory functional profile of microglia, which is characteristic for neuroinflammation in the clinical course of the disease, is more adequately reproduced.