Increase in <scp>GFAP</scp>‐positive astrocytes in histone demethylase <scp>GASC</scp>1/<scp>KDM</scp>4C/<scp>JMJD</scp>2C hypomorphic mutant mice

Sudo, Genki; Kagawa, Tetsushi; Kokubu, Yasuhiro; Inazawa, Johji; Taga, Tetsuya

doi:10.1111/gtc.12331

Cited by 16 publications

(16 citation statements)

References 25 publications

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“…With selective histone H3 lysine 36 demethylation and loss of RNA polymerase II recruitment in transcribed regions of GFAP, KDM4A/C represses astrocytic differentiation by control of elongation (Cascante et al, ). Consistently, in the brain of KDM4C hypomorphic mutant mice at 2–3 month‐old, an increase of GFAP‐positive astrocytes was widely observed in the forebrain (Sudo, Kagawa, Kokubu, Inazawa, & Taga, ). These facts suggest that demethylation of GFAP gene promoter can cause repression of GFAP expression.…”

Section: Expression Of Gfap and Its Regulationmentioning

confidence: 74%

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

Liu

et al. 2019

Glia

117

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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.

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Section: Expression Of Gfap and Its Regulationmentioning

confidence: 74%

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

Liu

et al. 2019

Glia

117

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“…However, neither neural genes nor neuronal master genes such as Sox1 , Pax6 , or Neurogenin were affected in HP1γ KO neurospheres, suggesting that HP1γ might primarily repress genes involved in the maturation of neuronal cells and not play a role in their fate determination. While H3K27me3 is important for the repression of neuronal genes, DNA methylation and H3K9me3 are crucial for repression of astrocyte‐specific genes during proliferation of neural stem cells and neuronal cell differentiation . Although HP1γ binds to H3K9me2/3, the expression of astrocyte‐specific genes did not change in HP1γ KO neurospheres compared with that in WT neurospheres.…”

Section: Discussionmentioning

confidence: 90%

“…While H3K27me3 is important for the repression of neuronal genes, DNA methylation and H3K9me3 are crucial for repression of astrocyte-specific genes during proliferation of neural stem cells and neuronal cell differentiation. [50][51][52][53] Although HP1γ binds to H3K9me2/3, the expression of astrocyte-specific genes did not change in HP1γ KO neurospheres compared with that in WT neurospheres. We speculate that HP1α and HP1β also bind to H3K9me2/3 and that they might compensate for the deficiency of HP1γ.…”

Section: Discussionmentioning

confidence: 93%

Heterochromatin protein 1γ deficiency decreases histone H3K27 methylation in mouse neurosphere neuronal genes

et al. 2020

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Heterochromatin protein (HP) 1γ, a component of heterochromatin in eukaryotes, is involved in H3K9 methylation. Although HP1γ is expressed strongly in neural tissues and neural stem cells, its functions are unclear. To elucidate the roles of HP1γ, we analyzed HP1γ ‐deficient (HP1γ KO) mouse embryonic neurospheres and determined that HP1γ KO neurospheres tended to differentiate after quaternary culture. Several genes normally expressed in neuronal cells were upregulated in HP1γ KO undifferentiated neurospheres, but not in the wild type (WT). Compared to that in the control neurospheres, the occupancy of H3K27me3 was lower around the transcription start sites (TSSs) of these genes in HP1γ KO neurospheres, while H3K9me2/3, H3K4me3, and H3K27ac amounts remained unchanged. Moreover, amounts of the H3K27me2/3 demethylases, UTX, and JMJD3, were increased around the TSSs of these genes. Treatment with GSK‐J4, an inhibitor of H3K27 demethylases, decreased the expression of genes upregulated in HP1γ KO neurospheres, along with an increase of H3K27me3 amounts. Therefore, in murine neurospheres, HP1γ protected the promoter sites of differentiated cell‐specific genes against H3K27 demethylases to repress the expression of these genes. A better understanding of central cellular processes such as histone methylation will help elucidate critical events such as cell‐specific gene expression, epigenetics, and differentiation.

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“…GFAP is an important cytoskeletal protein for astrocyte synthesis, which is now recognized as a characteristic astrocyte marker (33). Diabetes can affect astrocytes, resulting in alterations in GFAP expression.…”

Section: Discussionmentioning

confidence: 99%

“…Diabetes can affect astrocytes, resulting in alterations in GFAP expression. A previous study revealed that in diabetic rats, the expression of GFAP is decreased in the rat cortex, hippocampus and cerebellum, resulting in a decrease in the generation of blood vessels, the blood-brain barrier and the change in LTP, eventually leading to learning and memory dysfunction (33). It has also been reported that with the long-term stimulation of hyperglycemia, learning and memory functions in rats are gradually decreased, accompanied by the increased expression of GFAP in hippocampus; these results indicated that astrocytes are associated with anesthesia-induced cognitive dysfunction (34,35).…”

Section: Discussionmentioning

confidence: 99%

Protective effects of tetrahydropalmatine against ketamine-induced learning and memory injury via antioxidative, anti-inflammatory and anti-apoptotic mechanisms in mice

Zhang

Sha²,

Wang

et al. 2018

Mol Med Report

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Tetrahydropalmatine exerts numerous pharmacological activities, including analgesic and narcotic effects; anti-arrhythmic, blood pressure lowering and cardioprotective effects; protective effects against cerebral ischemia-reperfusion injury; inhibition of platelet aggregation; prevention of ulcerative diseases and inhibition of gastric acid secretion; antitumor effects; and beneficial effects on the withdrawal symptoms associated with drug addiction. The present study aimed to investigate the protective effects of tetrahydropalmatine against ketamine-induced learning and memory impairment in mice. The Morris water maze test and open field test were used to analyzed learning and memory impairment in mice. ELISA kits and western blotting were used to analyze oxidative stress, inflammation factors, caspease-3 and caspase-9, iNOS, glial fibrillary acidic protein (GFAP), glial cell-derived neurotrophic factor (GDNF), cytochrome c and phospholipase C (PLC)-γ1 protein expression. The results demonstrated that tetrahydropalmatine treatment significantly decreased escape latency in the learning phase and increased the number of platform site crossings in ketamine-induced mice. In addition, tetrahydropalmatine significantly inhibited oxidative stress, inflammation and acetylcholinesterase activity, and decreased acetylcholine levels in ketamine-induced mice. Tetrahydropalmatine also suppressed iNOS protein expression, weakened caspase-3 and caspase-9 activation, inhibited nuclear factor-κB, glial fibrillary acidic protein, cytochrome c and phospholipase C-γ1 protein expression, and induced glial cell-derived neurotrophic factor protein expression in ketamine-induced mice. Taken together, these results indicated that tetrahydropalmatine may protect against ketamine-induced learning and memory impairment in mice via antioxidative, anti-inflammatory and anti-apoptotic mechanisms. The present study provided an experimental basis for the clinical application of tetrahydropalmatine to reduce the severe side effects associated with ketamine therapy in future studies.

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Increase in GFAP‐positive astrocytes in histone demethylase GASC1/KDM4C/JMJD2C hypomorphic mutant mice

Cited by 16 publications

References 25 publications

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

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

Heterochromatin protein 1γ deficiency decreases histone H3K27 methylation in mouse neurosphere neuronal genes

Protective effects of tetrahydropalmatine against ketamine-induced learning and memory injury via antioxidative, anti-inflammatory and anti-apoptotic mechanisms in mice

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