Blocking transient receptor potential vanilloid 2 channel in astrocytes enhances astrocyte‐mediated neuroprotection after oxygen–glucose deprivation and reoxygenation

Abstract

Astrocytes play important roles in homeostatic regulation in the central nervous system and are reported to influence the outcome of ischemic injury. Regulating Ca signaling of astrocytes is a promising strategy for stroke therapy. Herein, we report for the first time that transient receptor potential vanilloid 2 (TRPV2), a Ca -permeable channel that is important in osmotic balance regulation, expresses in rat cortical astrocytes by immunofluorescence. Moreover, oxygen-glucose deprivation and reoxygenation (OGD/R) treatment enhanced the expression. The TRPV2 is functional because Ca imaging showed that activating the TRPV2 channel in cultured astrocytes increased intracellular Ca level and the increment of intracellular Ca level expanded when astrocytes were treated with OGD/R. Staining with 5-ethynyl-2'-deoxyuridine (EdU) revealed that while blocking the TRPV2, it promoted the proliferation of astrocytes. Additionally, blocking the TRPV2 in astrocytes increased the synthesis of nerve growth factor (NGF) mRNA and the secretion of NGF by real-time PCR and enzyme-linked immunosorbent assay respectively. We further found that the increased secretion of NGF could be reversed by c-JunN-terminalkinase (JNK) inhibitor and blocking the TRPV2 caused the phosphorylation of JNK. These indicated that blocking the TRPV2 induced NGF secretion via the mitogen-activated protein kinase (MAPK)-JNK signaling pathway. As the promoted proliferation of astrocytes and secretion of NGF were reported to have neuroprotective effects in the early stage of stroke, we concluded that targeting the TRPV2 channel in astrocytes might be a potential new therapeutic strategy in ischemic stroke.

N-Propargyl Caffeamide (PACA) Ameliorates Dopaminergic Neuronal Loss and Motor Dysfunctions in MPTP Mouse Model of Parkinson’s Disease and in MPP+-Induced Neurons via Promoting the Conversion of proNGF to NGF

“…Along this line, the present study showed that PACA effectively preserved the activation of PI3K/Akt, ERK1/2 CREB, and TrkA signaling pathways and maintained the levels of NGF protein in MPTP-treated mice. A recent study suggested that astrocytes produced NGF to support the survival of neurons against oxidative stress [44,45]. Consistently, the present study also showed that PACA might induce NGF expression in the entire midbrain cell population including astrocytes.…”

TRPV2 interacts with actin and reorganizes submembranous actin cytoskeleton

“…For example, of the small calcitonin gene-related peptide (CGRP) +ve neurons projecting to the skin, 11.6% were positive for TRPV2. Involvement of TRPV2 in neuro-protection have also been reported [55]. Here we demonstrate that TRPV2 plays important role in the regulation of neuritogenesis process.…”

TRPV2 activation reorganizes actin cytoskeleton, induces neurite initiation and branching by altering cAMP levels

“…For example, of the small CGRP +ve neurons projecting to the skin, 11.6% were positive for TRPV2. Involvement of TRPV2 in neuro-protection have also been reported 56 . Here we demonstrate that TRPV2 plays important role in the regulation of neuritogenesis process.…”