P38 MAPK is involved in enhanced NMDA receptor-dependent excitotoxicity in YAC transgenic mouse model of Huntington disease

Article ID	Journal	Published Year	Pages	File Type
6022684	Neurobiology of Disease	2012	11 Pages	PDF

Abstract

âº NMDAR-mediated pro-death pathways investigated in YAC128 Huntington disease mouse. âº Increased extrasynaptic PSD-95 and its interaction with GluN2B in YAC128 striatum. âº Cell death-associated proteins p38- and JNK-MAPK are activated in YAC128 striatum. âº NMDAR/PSD-95 complex required for NMDA-stimulated YAC128 striatal p38 activation. âº P38 inhibition or disruption of NMDAR/PSD-95 complex reduces YAC128 striatal death.

Keywords

NMDARs PFA aCSF NMDA N-methyl-d-aspartate PSD-95 p38 nNOS MSNs PolyQ YFP PBS htt striatal-enriched protein tyrosine phosphatase mHTT PSB Postsynaptic densities SynGAP MAGUKs YAC membrane-associated guanylate kinases NGS PSD PVDF GFP Jnk PBST ERK c-Jun N-terminal kinase MAPK NMDA receptor ROS sodium dodecyl sulfate-polyacrylamide gel electrophoresis SDS-PAGE excitotoxicity Huntington disease TUNEL standard error of the mean Room temperature polyvinylidene difluoride DIV days in vitro normal goat serum neuronal nitric oxide synthase Co-IP artificial cerebrospinal fluid Phosphate-buffered saline SEM human immunodeficiency virus-type 1 medium spiny neurons Huntingtin mutant Huntingtin Co-Immunoprecipitation HIV-1 paraformaldehyde yellow fluorescent protein green fluorescent protein mitogen-activated protein kinase Extracellular signal-regulated protein kinase Polyglutamine Yeast artificial chromosome STEP Reactive oxygen species NMDA receptors