Truncated Metabotropic glutamate receptor 1 worsens long-term neurological outcomes in a rat model of subarachnoid hemorrhage

Objective Truncation of mGluR1 occurs in cerebrospinal fluid (CSF) from aneurysmal subarachnoid hemorrhage (aSAH) patients, but the effect of truncated mGluR1 on brain injury is still unclear. This study aims to explore the site of mGluR1 breakage in CSF and investigate the effect of truncated mGluR1 on a rat SAH model. Methods The CSF of aSAH patients was immunoprecipitated with mGluR1 antibody, and the target bands were collected for protein sequencing. Immunofluorescence staining was used to evaluate mGluR1 cleavage in SAH rat model. Neurological function was evaluated using foot-fault test, forelimb placement test, rotarod test, and Morris water maze test. The effects on hippocampal neurons were evaluated using HE, Nissl, TUNEL staining and NeuN immunostaining. Results The site of mGluR1 truncation in the CSF of aSAH patients may be Ser936. In the SAH model of rats, there was no truncated mGluR1 in the sham group, while the basal cortex and hippocampal CA1 regions were present in the 24 h and 72 h groups after SAH. Overexpression of mGluR1-Ser936Δ causes decrease in the number of neurons, morphological abnormalities, and loss of Nissl bodies in hippocampus, and exacerbates SAH-induced sensory motor and spatial cognitive dysfunction. Conclusion Truncated mGluR1 exacerbates long-term neurological dysfunction after experimental SAH.