Chronic stress as a risk factor for Alzheimer's disease: Roles of microglia-mediated synaptic remodeling, inflammation, and oxidative stress

Abstract

Microglia are the predominant immune cells of the central nervous system (CNS) that exert key physiological roles required for maintaining CNS homeostasis, notably in response to chronic stress, as well as mediating synaptic plasticity, learning and memory. The repeated exposure to stress confers a higher risk of developing neurodegenerative diseases including sporadic Alzheimer's disease (AD). While microglia have been causally linked to amyloid beta (Aβ) accumulation, tau pathology, neurodegeneration, and synaptic loss in AD, they were also attributed beneficial roles, notably in the phagocytic elimination of Aβ. In this review, we discuss the interactions between chronic stress and AD pathology, overview the roles played by microglia in AD, especially focusing on chronic stress as an environmental risk factor modulating their function, and present recently-described microglial phenotypes associated with neuroprotection in AD. These microglial phenotypes observed under both chronic stress and AD pathology may provide novel opportunities for the development of better-targeted therapeutic interventions.

Microglia in neuropathology caused by protozoan parasites

“…(), Tay et al . () and Bisht, Sharma & Tremblay (). In this review, we focus our attention on the role of microglia in parasitosis induced by protozoan parasites.…”

“…Microglial cells play prominent roles in brain development, homeostasis and aging, brain immunology, neurodegeneration, neuroinflammation and cellular plasticity. For in-depth reviews of these topics, see Miyamoto et al (2013), Erny, Hrabě de Angelis & Prinz (2017), Mosser et al (2017), Tay et al (2017) and Bisht, Sharma & Tremblay (2018). In this review, we focus our attention on the role of microglia in parasitosis induced by protozoan parasites.…”

Chronic Mild Stress Modified Epigenetic Mechanisms Leading to Accelerated Senescence and Impaired Cognitive Performance in Mice

“…However, when stress is prolonged it has been shown to decrease synaptic plasticity [8], alter hippocampal volume [9,10] and neurotransmitters [11], and may lead to AD [12]. In particular, chronic stress is associated with increased Aβ deposits and hyperphosphorylated Tau [13].Oxidative stress (OS) and inflammation are deeply involved in age-related deleterious disorders. Along with the aging process, several factors, such as a naturally decreased capacity of the antioxidant enzymes system, create an imbalance between antioxidant mechanisms and reactive oxygen system (ROS)-production equilibrium, accumulating ROS beyond the detoxifying capacity of the antioxidant system resulting in OS, eventually causing cellular damage that can no longer be repaired by internal mechanisms, and finally causing dysfunction of the system [14].…”

Chronic Oral Administration of Tenebrio molitor Extract Exhibits Inhibitory Effect on Glucocorticoid Receptor Overexpression in the Hippocampus of Ovariectomy‐Induced Estrogen Deficient Mice

“…Apolipoprotein E (ApoE), a major component of low‐density lipoprotein (LDL) and very low‐density lipoprotein (VLDL) circulating in blood, mediates uptake of these lipoproteins into cells by binding to ApoE receptors, principally the LDL receptor (Goldstein & Brown, ). However, ApoE has three different isoforms, and among the isoforms, ApoE4 may be closely related with lower bone formation as well as increased risk of osteoporosis and bone fractures, whereas ApoE3; to decrease lowering BMD in postmenopausal women, and its presence seemed to lower the incidence of bone fractures in patients with osteoporosis (Souza et al., ), and plays a role in making neurodegenerative disease, memory and cognitive disorders and Alzheimer's disease highly resistant (Bisht, Sharma, & Tremblay, ; Noguchi et al., ; Raber et al., ; Riedel et al., ). Therefore, according to these preliminary studies, we have demonstrated efficacy of anti‐osteoporosis efficacy and attenuated hyper‐active HPA axis regulation in the chronic administration of TM extract used in this study, and TM extract can be expected to mitigate the discomfort associated with diseases and hormone disorders in women after menopause.…”