NEK6 is an injury‐responsive kinase cooperating with STAT3 in regulation of reactive astrogliosis

Glia ◽  
2021 ◽  
Author(s):  
Ying Yu ◽  
Tianjin Shen ◽  
Xiaoling Zhong ◽  
Lei‐Lei Wang ◽  
Wenjiao Tai ◽  
...  
Keyword(s):  
Reactive Astrogliosis

scholarly journals CDDO-Me Distinctly Regulates Regional Specific Astroglial Responses to Status Epilepticus via ERK1/2-Nrf2, PTEN-PI3K-AKT and NFκB Signaling Pathways

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1026
Author(s):  
Ji-Eun Kim ◽  
Hana Park ◽  
Tae-Cheon Kang
Keyword(s):  
Status Epilepticus ◽  
Signaling Pathways ◽  
Seizure Activity ◽  
Molecular Layer ◽  
Antioxidant Properties ◽  
Acid Methyl Ester ◽  
Related Factor ◽  
Nuclear Factor ◽  
Reactive Astrogliosis ◽  
Nrf2 Expression

2-Cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me) is a triterpenoid analogue of oleanolic acid. CDDO-Me shows anti-inflammatory and neuroprotective effects. Furthermore, CDDO-Me has antioxidant properties, since it activates nuclear factor-erythroid 2-related factor 2 (Nrf2), which is a key player of redox homeostasis. In the present study, we evaluated whether CDDO-Me affects astroglial responses to status epilepticus (SE, a prolonged seizure activity) in the rat hippocampus in order to understand the underlying mechanisms of reactive astrogliosis and astroglial apoptosis. Under physiological conditions, CDDO-Me increased Nrf2 expression in the hippocampus without altering activities (phosphorylations) of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), phosphatidylinositol-3-kinase (PI3K), and AKT. CDDO-Me did not affect seizure activity in response to pilocarpine. However, CDDO-Me ameliorated reduced astroglial Nrf2 expression in the CA1 region and the molecular layer of the dentate gyrus (ML), and attenuated reactive astrogliosis and ML astroglial apoptosis following SE. In CA1 astrocytes, CDDO-Me inhibited the PI3K/AKT pathway by activating PTEN. In contrast, CDDO-ME resulted in extracellular signal-related kinases 1/2 (ERK1/2)-mediated Nrf2 upregulation in ML astrocytes. Furthermore, CDDO-Me decreased nuclear factor-κB (NFκB) phosphorylation in both CA1 and ML astrocytes. Therefore, our findings suggest that CDDO-Me may attenuate SE-induced reactive astrogliosis and astroglial apoptosis via regulation of ERK1/2-Nrf2, PTEN-PI3K-AKT, and NFκB signaling pathways.

Zinc induces reactive astrogliosis through ERK dependent activation of Stat3 and promotes synaptic degeneration

2021 ◽  
Author(s):  
Huiliang Zhang ◽  
Mengzhe Yang ◽  
Xiaochuan Wang ◽  
Hui Wei ◽  
Min Du ◽  
...  
Keyword(s):  
Reactive Astrogliosis ◽  
Synaptic Degeneration

Reactive astrogliosis induces astrocytic differentiation of adult neural stem/progenitor cells in vitro

2006 ◽  
Vol 84 (7) ◽  
pp. 1415-1424 ◽  
Author(s):  
J. Faijerson ◽  
R.B. Tinsley ◽  
K. Apricó ◽  
A. Thorsell ◽  
C. Nodin ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Reactive Astrogliosis ◽  
Astrocytic Differentiation ◽  
Neural Stem Progenitor Cells

scholarly journals Sonic hedgehog stimulates neurite outgrowth in a mechanical stretch model of reactive-astrogliosis

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Antonio Berretta ◽  
Emma K. Gowing ◽  
Christine L. Jasoni ◽  
Andrew N. Clarkson
Keyword(s):  
Neurite Outgrowth ◽  
Sonic Hedgehog ◽  
Mechanical Stretch ◽  
Reactive Astrogliosis

ChK1 Activation Induces Reactive Astrogliosis Through CIP2A/PP2A/STAT3 Pathway In Alzheimer's Disease

2021 ◽  
Author(s):  
Ying Zhou ◽  
Xiaoyuan Liu ◽  
Shuqing Ma ◽  
Dichen Yang ◽  
Nan Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dna Damage ◽  
Cognitive Deficits ◽  
Immunofluorescent Staining ◽  
Experimental Conditions ◽  
Stat3 Pathway ◽  
Reactive Astrogliosis

Abstract Background: In Alzheimer’s disease (AD), activation of astrocyte participates in the development of neurodegenerative diseases through neuroinflammation and disturbs glia-neuron interaction. Cancerous Inhibitor of PP2A (CIP2A) is an endogenous PP2A inhibitor. CIP2A upregulation specifically in astrocytes causes reactive astrogliosis, synaptic degeneration and cognitive deficits. However, the underlying mechanism of CIP2A upregulation remains unclear. Methods: In 3xTg-AD mice, we determined ChK1 was activated and related to DNA damage upregulating CIP2A by WB. We transfected EGFP-ChK1 plasmid into HEK293-T cell to determine ChK1 induces CIP2A upregulation and PP2A inhibition. We incubated Aβ and infected GFAP-ChK1-LV into primary astrocytes to confirm the signaling pathway in astrocytes and astrogliosis in AD. GFAP-ChK1-AAV was injected into C57/BL6 mice to induce specific expression of target protein in astrocytes. ChK1 inhibitor (SB) was performed to reverse the ChK1 activity. Outcomes were assessed using molecular (immunofluorescent staining, Western Blot and Golgi staining) measures to estimate symptomatic pathology and behavioral (NORT, OLT, MWM and FCT) measures to assess cognitive function. For most experiments, subjects were randomly assigned to experimental groups, and data were collected under blinded experimental conditions.Results: We demonstrated that DNA damage related Checkpoint kinase 1 (ChK1) was activated in 3xTg-AD mice. ChK1-mediated CIP2A overexpression drove inhibition of PP2A and activated STAT3, then led to reactive astrogliosis and neurodegeneration in vitro. Infection of mouse brain with GFAP-ChK1-AAV induced AD-like cognitive deficits and exacerbated AD pathologies in vivo. In conclusion, we showed that ChK1 activation induced reactive astrogliosis, degeneration of neurons and deterioration of AD through CIP2A-PP2A-STAT3 pathway, and inhibiting ChK1 might be a potential therapeutic approach for AD treatment.Conclusions: These results suggest that ChK1 is upregulated in 3xTg-AD mice, ChK1-mediated CIP2A overexpression drives inhibition of PP2A and activates STAT3, then leads to reactive astrogliosis, neurodegeneration and AD-like cognitive deficits in vitro and in vivo.

Reactive Astrogliosis in the Injured and Postischemic Brain

2003 ◽  
pp. 233-250 ◽  
Author(s):  
Ronald Jabs ◽  
Lane K. Bekar ◽  
Wolfgang Walz
Keyword(s):  
Reactive Astrogliosis
Sign in / Sign up

Export Citation Format

Share Document