Peroxisome proliferator‐activated receptor gamma participates in the acquisition of brain ischemic tolerance induced by ischemic preconditioning via glial glutamate transporter 1 in vivo and in vitro

Abstract

Glial glutamate transporter 1 (GLT‐1) plays a vital role in the induction of brain ischemic tolerance (BIT) by ischemic preconditioning (IPC). However, the mechanism still needs to be further explained. The aim of this study was to investigate whether peroxisome proliferator‐activated receptor gamma (PPARγ) participates in regulating GLT‐1 during the acquisition of BIT induced by IPC. Initially, cerebral IPC induced BIT and enhanced PPARγ and GLT‐1 expression in the CA1 hippocampus in rats. The ratio of nuclear/cytoplasmic PPARγ was also increased. At the same time, the up‐regulation of PPARγ expression in astrocytes in the CA1 hippocampus was revealed by double immunofluorescence for PPARγ and glial fibrillary acidic protein. Then, the mechanism by which PPARγ regulates GLT‐1 was studied in rat cortical astrocyte‐neuron cocultures. We found that IPC [45 min of oxygen glucose deprivation (OGD)] protected neuronal survival after lethal OGD (4 h of OGD), which usually leads to neuronal death. The activation of PPARγ occurred earlier than the up‐regulation of GLT‐1 in astrocytes after IPC, as determined by western blot and immunofluorescence. Moreover, the preadministration of the PPARγ antagonist T0070907 or PPARγ siRNA significantly attenuated GLT‐1 up‐regulation and the neuroprotective effects induced by IPC in vitro. Finally, the effect of the PPARγ antagonist on GLT‐1 expression and BIT was verified in vivo. We observed that the preadministration of T0070907 by intracerebroventricular injection dose‐dependently attenuated the up‐regulation of GLT‐1 and BIT induced by cerebral IPC in rats. In conclusion, PPARγ participates in regulating GLT‐1 during the acquisition of BIT induced by IPC. Cover Image for this issue: doi: . Open Science: This manuscript was awarded with the Open Materials Badge For more information see: https://cos.io/our-services/open-science-badges/

Alpha-Asaronol Alleviates Dysmyelination by Enhancing Glutamate Transport Through the Activation of PPARγ-GLT-1 Signaling in Hypoxia-Ischemia Neonatal Rats

“…As one of the target genes of PPARγ, GLT-1 is regulated by PPARγ during the acquisition of brain ischemic tolerance ( Romera et al, 2007 ) and is involved in neuroprotection by increasing glutamate uptake in ischemic preconditioning rats ( Zhao et al, 2019 ). Our previous study also found that α-asaronol could promote the mRNA expression of PPARγ in zebrafish ( Jin et al, 2020 ).…”

LncRNA BIRF Promotes Brain Ischemic Tolerance Induced By Cerebral Ischemic Preconditioning Through Upregulating GLT-1 via Sponging miR-330-5p

“…We have previously reported that ischemic preconditioning (IPC)-induced BIT [ 28 ]. To further explore the role of astrocytes in the process, in this study, cerebral cortical astrocytes and neurons of rats were co-cultured, the astrocytes of the co-cultured cell model pretreated by IPC (45 min of OGD) were subjected to lncRNA high-throughput sequencing (RNA-seq).…”

Activation of astroglial CB1R mediates cerebral ischemic tolerance induced by electroacupuncture

“…Several studies have demonstrated that interactions between astrocytes and surrounding cells can influence neuronal activity and brain injury outcomes. [53][54][55][56][57][58] However, the function of astrocytes in EA-induced neuroprotection is unclear. Our previous finding demonstrated that long-term depression induced by endogenous cannabinoids produced neuroprotective effects via astroglial CB 1 R after stroke in rodents, 29 which also indicates that astroglia are of great importance in neuroprotection.…”