CELSR1 Promotes Neuroprotection in Cerebral Ischemic Injury Mainly through the Wnt/PKC Signaling Pathway

Abstract

Cadherin epidermal growth factor (EGF) laminin G (LAG) seven-pass G-type receptor 1 (CELSR1) is a member of a special subgroup of adhesion G protein-coupled receptors. Although Celsr1 has been reported to be a sensitive gene for stroke, the effect of CELSR1 in ischemic stroke is still not known. Here, we investigated the effect of CELSR1 on neuroprotection, neurogenesis and angiogenesis in middle cerebral artery occlusion (MCAO) rats. The mRNA expression of Celsr1 was upregulated in the subventricular zone (SVZ), hippocampus and ischemic penumbra after cerebral ischemic injury. Knocking down the expression of Celsr1 in the SVZ with a lentivirus significantly reduced the proliferation of neuroblasts, the number of CD31-positive cells, motor function and rat survival and increased cell apoptosis and the infarct volume in MCAO rats. In addition, the expression of p-PKC in the SVZ and peri-infarct tissue was downregulated after ischemia/ reperfusion. Meanwhile, in the dentate gyrus of the hippocampus, knocking down the expression of Celsr1 significantly reduced the proliferation of neuroblasts; however, it had no influence on motor function, cell apoptosis or angiogenesis. These data indicate that CELSR1 has a neuroprotective effect on cerebral ischemia injury by reducing cell apoptosis in the peri-infarct cerebral cortex and promoting neurogenesis and angiogenesis, mainly through the Wnt/PKC pathway.

New Insights in Molecular Mechanisms and Pathophysiology of Ischemia-Reperfusion Injury 2.0: An Updated Overview

“…Moreover, there is growing evidence in the brain that factors such as CELSR1 (Cadherin epidermal growth factor (EGF) laminin G (LAG) seven-pass G-type receptor) are responsible for neuroprotective effects on cerebral ischemia injury [19]. This is consistent with the recent investigations of Schuhmann, M.K.…”

Anticonvulsive and Neuroprotective Effects of Eupafolin in Rats Are Associated with the Inhibition of Glutamate Overexcitation and Upregulation of the Wnt/β-Catenin Signaling Pathway

“…The inhibition of PKC or Akt that accompanies neuronal death has been observed in the brain under excitotoxic conditions, and this excitotoxic brain damage also appears to be prevented by PKC or Akt activation. 47,48 In addition, PKC has been found to phosphorylate the C-terminal intracellular regulatory domain of the AMPA receptor subunit, including GluR2, 49 and this PKC-GluR2 axis is known to play a neuroprotective role in glutamate-induced neurotoxicity. 50 In our study, we found that the KA-induced decreases in the phosphorylation of the AMPA receptor subunit GluR2 and PKCα were significantly increased by eupafolin, implying that the PKC-GluR2 axis is also involved in the anticonvulsant and neuroprotective effects of eupafolin.…”

Antagonistic effects of IL-17 and Astragaloside IV on cortical neurogenesis and cognitive behavior after stroke in adult mice through Akt/GSK-3β pathway

“…So, the future research of stroke must expand its horizon to find new strategies. Neurogenesis is a promising step toward the recovery and restoration of brain function after stroke and other neurogenerative diseases [39][40][41] . Our study demonstrated that in an early stage of ischemic stroke, IL-17, as an important indicator of poor prognosis, was involved in the proliferation relevant signal pathway-PI3K/Akt pathway, and responsible for suppressing local NSCs stemness and neurogenesis, as well as infraction area.…”