Astrocyte, a Promising Target for Mood Disorder Interventions

Abstract

Mood disorders have multiple phenotypes and complex underlying biological mechanisms and, as such, there are no effective therapeutic strategies. A review of recent work on the role of astrocytes in mood disorders is thus warranted, which we embark on here. We argue that there is tremendous potential for novel strategies for therapeutic interventions based on the role of astrocytes. Astrocytes are traditionally considered to have supporting roles within the brain, yet emerging evidence has shown that astrocytes have more direct roles in influencing brain function. Notably, evidence from postmortem human brain tissues has highlighted changes in glial cell morphology, density and astrocyte-related biomarkers and genes following mood disorders, indicating astrocyte involvement in mood disorders. Findings from animal models strongly imply that astrocytes not only change astrocyte morphology and physiological characteristics but also influence neural circuits via synapse structure and formation. This review pays particular attention to interactions between astrocytes and neurons and argues that astrocyte dysfunction affects the monoaminergic system, excitatory–inhibitory balance and neurotrophic states of local networks. Together, these studies provide a foundation of knowledge about the exact role of astrocytes in mood disorders. Importantly, we then change the focus from neurons to glial cells and the interactions between the two, so that we can understand newly proposed mechanisms underlying mood disorders, and to identify more diagnostic indicators or effective targets for treatment of these diseases.

Experimental Traumatic Brain Injury Induces Chronic Glutamatergic Dysfunction in Amygdala Circuitry Known to Regulate Anxiety-Like Behavior

“…Studies report that GFAP levels can mediate expression of glutamate transporters, such that low levels of GFAP are associated with mood disorders, activation of astrocytes influence neurotransmission, and microglial activation triggers astrocytemediated modulation of excitatory neurotransmission (Pascual et al, 2012). In evaluating GFAP immunohistochemistry, increased levels of GFAP can be interpreted as a presence of activated astrocytes or increased number of astrocytes, whereas decreased levels can indicate a downregulation of GFAP and/or reduced number of astrocyte (reviewed in Hughes et al, 2004;Rajkowska and Miguel-Hidalgo, 2007;Zhou et al, 2019). Analysis of GFAP density in the CeA revealed no differences over time post-injury, in contrast to our previous work in the BLA, where morphology and increased GFAP staining indicated activated astrocytes at 7 DPI (Hoffman et al, 2017).…”

Parvalbumin interneurons in the nucleus accumbens regulate impairment of risk avoidance in DISC1 transgenic mice

“…Many transgenic rodent models have been generated to manipulate the function of DISC1 gene [4][5][6]. Many studies have shown that DISC1 transgenic rodents show abnormal cognitive function, including object recognition memory deficits, working memory deficits, and social recognition deficits [7,8]. These cognitive deficits are consistent with those found in human patients with mental disorders [9][10][11].…”

“…As an important hub protein, DISC1 can interact with a number of synaptic or cytoskeletal molecules and modulate many cellular functions, such as synaptic plasticity [51] and neurogenesis [52,53]. As such, different mutant models (e.g., DISC1 mutation overexpressed model [8]) may influence DISC1 function to varying degrees and lead to different phenotypes. In this article, we used N-terminal fragment DISC1 transgenic mice.…”

Zuogui Jiangtang Jieyu Decoction Ameliorates Depression-Like Behavior in Diabetic Rats via Activation of Neuronal and Astrocytic IR/IRS-1 Signaling Pathway

“…Clinical study reveals that astrocyte is relevant to reduced volume of hippocampus in subjects with major depression [10]. In fact, the damage of astrocyte is not only existed in depression, but also found in mood disorder and cognitive impairment in diabetes.…”

“…Although most studies suggest that the cell respond to insulin in hippocampus is mainly neurons, recent study showed that insulin can act on astrocytes (a gliocyte in hippocampus) and produces physiological effects [9]. And astrocyte may be a "hopeful" target for intervention of emotional abnormalities [10].…”