Abstract
Astrocytes respond to central nervous system (CNS) insults with varieties of changes, such as cellular hypertrophy, migration, proliferation, scar formation, and upregulation of glial fibrillary acidic protein (GFAP) expression. While scar formation plays a very important role in wound healing and prevents further bleeding by forming a physical barrier, it is also one of key features of CNS injury, resulting in glial scar formation (astrogliosis), which is closely related to treatment resistant epilepsy, chronic pain, and other devastating diseases. Therefore, slowing the astrocytic activation process may give a time window of axonal growth after the CNS injury. However, the underlying mechanism of astrocytic activation remains unclear, and there is no effective therapeutic strategy to attenuate the activation process. Here, we found that methimazole could effectively inhibit the GFAP expression in physiological and pathological conditions. Moreover, we scratched primary cultures of cerebral cortical astrocytes with and without methimazole pretreatment and investigated whether methimazole could slow the healing process in these cultures. We found that methimazole could inhibit the GFAP protein expression in scratched astrocytes and prolong the latency of wound healing in cultures. We also measured the phosphorylation of extracellular signal-regulated kinase (ERK) in these cultures and found that methimazole could significantly inhibit the scratch-induced GFAP upregulation. For the first time, our study demonstrated that methimazole might be a possible compound that could inhibit the astrocytic activation following CNS injury by reducing the ERK phosphorylation in astrocytes.
Highlights
Astrocytes are the most abundant cell type in the central nervous system (CNS), which can support the neighbouring neurons and integrate the nervous communication unit in the form of a “tripartite synapse” [1]
We investigate whether methimazole could exert direct effect on the activation process of the astrocyte in an in vitro scratch wound model by exploring the effects of methimazole on the glial fibrillary acidic protein (GFAP) protein expression and wound healing
The increase of the GFAP protein level could be inhibited by the pretreatment of methimazole in the cultured astrocytes
Summary
Astrocytes are the most abundant cell type in the CNS, which can support the neighbouring neurons and integrate the nervous communication unit in the form of a “tripartite synapse” [1]. In CNS, astrocytes undergo extensive physiological and morphological changes following insults, including trauma and surgery [3]. Astrogliosis could become a detrimental process for the neuronal functional recovery if the cellular reaction occurs in a very fast way, forming a physical barrier that blocks the possible neuroregeneration [6]. Astrogliosis could inhibit adaptive neural plasticity that is an essential process of neuronal recovery following injury [5]. Identifying the possible compounds that could slow down the activation process of the astrocyte may open a new road for neuronal functional recovery and provide more information to preclinical studies, such as in animal models
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