Neurochemical regulation of the expression and function of glial fibrillary acidic protein in astrocytes

Abstract

Glial fibrillary acidic protein (GFAP), a type III intermediate filament, is a marker of mature astrocytes. The expression of GFAP gene is regulated by many transcription factors (TFs), mainly Janus kinase‐2/signal transducer and activator of transcription 3 cascade and nuclear factor κ‐light‐chain‐enhancer of activated B cell signaling. GFAP expression is also modulated by protein kinase and other signaling molecules that are elicited by neuronal activity and hormones. Abnormal expression of GFAP proteins occurs in neuroinflammation, neurodegeneration, brain edema‐eliciting diseases, traumatic brain injury, psychiatric disorders and others. GFAP, mainly in α‐isoform, is the major component of cytoskeleton and the scaffold of astrocytes, which is essential for the maintenance of astrocytic structure and shape. GFAP also has highly morphological plasticity because of its quick changes in assembling and polymerizing states in response to environmental challenges. This plasticity and its corresponding cellular morphological changes endow astrocytes the functions of physical barrier between adjacent neurons and stabilizer of extracellular environment. Moreover, GFAP colocalizes and even molecularly associates with many functional molecules. This feature allows GFAP to function as a platform for direct interactions between different molecules. Last, GFAP involves transportation and localization of other functional proteins and thus serves as a protein transport guide in astrocytes. This guiding role of GFAP involves an elastic retraction and extension cytoskeletal network that couples with GFAP reassembling, transporting, and membrane protein recycling machinery. This paper reviews our current understanding of the expression and functions of GFAP as well as their regulation.

Evaluation of neurological effects of cerium dioxide nanoparticles doped with different amounts of zirconium following inhalation exposure in mouse models of Alzheimer's and vascular disease

“…Protein expression of ionized calcium-binding adapter molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) was evaluated by Western blot to address whether the exposures to the CeO 2 NPs resulted in neuroinflammation and oxidative stress. Iba-1 and GFAP represent well-established markers of activated microglia ( Kovacs, 2017 ; Sasaki et al 2001 ) and mature astrocytes in neuroinflammation ( Li et al 2020 ; Sofroniew and Vinters, 2010 ), respectively. The transcription factor Nrf2 is a master regulator of cellular responses to oxidants via its activation of oxidative stress response genes including HO-1.…”

Astrocytes in the nucleus of the solitary tract: Contributions to neural circuits controlling physiology

“…Astrocytes show regional variations in the expression of the cytoskeletal glial fibrillary acidic protein (GFAP), which is dynamically regulated in response to local variations in the brain microenvironment [55] , [56] , [57] . For example cortical astrocytes show low basal GFAP expression but dramatically upregulate this protein in response to tissue injury, suggesting that this change serves a reactive and possibly neuroprotective role [58] .…”

“…Notably in rats, within the NTS the astrocytes are smaller, have a simpler morphology, and greater overlapping domains than other brainstem autonomic nuclei [62] . Since GFAP is not a uniformly expressed astrocyte marker [ 55 , 56 ] and is dynamically regulated [ 57 , 58 ], some studies have utilized other markers, including the calcium binding protein S100b [27] .…”

Development of a sexual dimorphism in a central pattern generator driving a rhythmic behavior: The role of glia‐mediated potassium buffering in the pacemaker nucleus of the weakly electric fishApteronotus leptorhynchus

“…It is likely that the increased expression in GFAP reflects the changes in size and shape of these astrocytes in females, compared to males, or after β‐estradiol treatment. GFAP has been implicated in intermediate filament network dynamics, including changes in cell morphology (Li et al, 2019; Moeton et al, 2016).…”