%0 Journal Article
%T TAT-mGluR1 Attenuation of Neuronal Apoptosis through Prevention of MGluR1¦Á Truncation after Experimental Subarachnoid Hemorrhage
%J -
%D 2019
%R https://doi.org/10.1021/acschemneuro.8b00531
%X Excessive glutamate-mediated overactivation of metabotropic glutamate receptor 1 (mGluR1) plays a leading role in neuronal apoptosis following subarachnoid hemorrhage (SAH). TAT-mGluR1, a fusion peptide consisting of a peptide spanning the calpain cleavage site of mGluR1¦Á and the trans-activating regulatory protein (TAT) of HIV, effectively blocks mGluR1¦Á truncation and protects neurons against excitotoxic damage. This study investigated the effects of TAT-mGluR1 on neuronal apoptosis in the rat SAH model. Here, we report that SAH caused activation of calpain and truncation of mGluR1¦Á; intraperitoneally administered TAT-mGluR1 did not affect calpain activity, while it blocked truncation of mGluR1¦Á after SAH. Intraperitoneally administered FITC-labeled TAT-mGluR1 was colocalized with mGluR1¦Á in thecortex after SAH. Furthermore, TAT-mGluR1 significantly improved the neurological deficit, increased p-PI3K, p-Akt, and p-GSK3¦Â, downregulated Bax, upregulated Bcl-2, and reduced cortical apoptosis in the basal cortex at 24 h after SAH. These findings indicated that TAT-mGluR1 acted against SAH-induced cell apoptosis through preventing mGluR1¦Á truncation
%U https://pubs.acs.org/doi/10.1021/acschemneuro.8b00531