The role of metabotropic glutamate receptor 5 in cerebral ischemia

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Group I metabotropic glutamate receptor 5 (mGluR5), belongs to G-protein coupled receptors family and plays important roles in CNS disorders including Fragile X syndrome, drug addiction, epilepsy and stroke. Our previous study showed that inhibition of Group I mGluRs, including mGluR1 and mGluR5, can reduce acute brain damage and improve long-term outcomes after ischemia. However, the contribution of mGluR5 to ischemic injury remains to be determined. In this study, we used mGluR5 knockout (KO) mice to examine whether genetic deletion of mGluR5 will affect brain damage and functional recovery following stroke. Using a photothrombosis induced ischemia model, we found that female mGluR5 KO mice exhibited larger infarct volume after ischemia compared to wild type females, whereas male wild type and mGluR5 KO mice have similar infarctions. Consistently, behavioral assessments following ischemia indicated that female mGluR5 KO mice showed worse performance in hanging wire test and adhesive removal test while there is no significant difference in these tests between male wild type and mGluR5 KO mice. In addition, we observed a difference in neuronal degeneration in female wild type and mGluR5 KO mice but no difference in apoptosis between wild type and mGluR5 KO mice from both genders. Taken together, our results demonstrate that mGluR5 plays an important role in ischemia in female mice and suggest that male and female may function differently after ischemia.