Emerging Roles of Astrocytes in Neuro-Vascular Unit and the Tripartite Synapse With Emphasis on Reactive Gliosis in the Context of Alzheimer’s Disease

Abstract

Astrocytes, which are five-fold more numerous than neurons in the central nervous system (CNS), are traditionally viewed to provide simple structural and nutritional supports for neurons and to participate in the composition of the blood brain barrier (BBB). In recent years, the active roles of astrocytes in regulating cerebral blood flow (CBF) and in maintaining the homeostasis of the tripartite synapse have attracted increasing attention. More importantly, astrocytes have been associated with the pathogenesis of Alzheimer’s disease (AD), a major cause of dementia in the elderly. Although microglia-induced inflammation is considered important in the development and progression of AD, inflammation attributable to astrogliosis may also play crucial roles. A1 reactive astrocytes induced by inflammatory stimuli might be harmful by up-regulating several classical complement cascade genes thereby leading to chronic inflammation, while A2 induced by ischemia might be protective by up-regulating several neurotrophic factors. Here we provide a concise review of the emerging roles of astrocytes in the homeostasis maintenance of the neuro-vascular unit (NVU) and the tripartite synapse with emphasis on reactive astrogliosis in the context of AD, so as to pave the way for further research in this area, and to search for potential therapeutic targets of AD.

Pathology of inflammatory diseases of the nervous system: Human disease versus animal models

“…In later stages of the inflammatory process astrocytes become a prominent source of anti‐inflammatory or immune regulatory molecules, such as interleukin 10 or TGF‐ß, as even shown in the human brain (Machado‐Santos et al, ). In line with these observations, polarization into proinflammatory A1 and anti‐inflammatory A2 astrocytes, which is similar to M1 and M2 polarization of microglia, has been described in vitro and in vivo (Liu, Yang, Ju, Wang, & Thang, ), although with different profiles between mouse and human astrocytes (Tarassishin, Suh, & Lee, ).…”

Sleep-like behavior is a fundamental property of the tripartite synapse

“…4,8 In more recent years, the crucial role of astrocytes in neuronal synaptic transmission has been elucidated, giving rise to the concept of the “tripartite synapse”. 1,2,9…”

“… The tripartite synapse, consisting of the presynaptic neuron, post-synaptic neuron, and an astrocyte, is considered to be the main locus of signaling between neurons in the brain. 1,2 Neurotransmission is energetically very expensive 3,4 , and the primary neurotransmitter utilized for signaling is glutamate. It has been found that glutamate is also used as a substrate for energy generation.…”

Lipotoxicity, neuroinflammation, glial cells and oestrogenic compounds

“…It has been shown that human astrocytes can secrete molecules associated with inflammation such as interleukins, as well as chemotactic factors such as MCP‐1, macrophage inflammatory protein‐1α and interferon‐γ‐inducible protein 10 . It was reported that astrocytes are actively involved in the secretion of pro‐inflammatory molecules IL‐6 and interferon (INF)γ . Additionally, oestradiol has the ability to decrease the secretion of these inflammatory molecules in an oxidative model mediated by H 2 O 2 following stimulation with lipopolysaccharide (LPS), for which the response is associated with the NF‐κB pathway .…”