Changes in NMDAR subunits levels in the cerebral cortex of zQ175 mice

LUISINA CASTELLARI; JULIETA SABA; FEDERICO LÓPEZ COUSELO; MARÍA VERÓNICA BAEZ; CARLA CARUSO

Buenos Airesq

Congreso; XXVII Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias; 2022

Sociedad Argentina de Investigación en Neurociencias

Huntington’s disease (HD) is a predominantly heritable neurodegenerative disorder caused by a mutation in thehuntingtin gene, which leads to expansion of the CAG repeat within exon 1 of the protein. Synaptic signaling alterationsunderlie the behavioral and neuropathological changes observed during HD. In particular, there is increased corticalexcitability in presymptomatic patients. Dysregulation of glutamatergic signaling is known to play an important role in thisdisease and may contribute to early synaptic dysfunction observed in HD. In this work, using a zQ175 knock-in mousemodel, we characterized NMDA receptor levels in the cortex and striatum of Huntington (zQ175) and wild-type (WT) miceat 4 and 8 months of age. Preliminary results suggest that GluN1 levels are increased in the cerebral cortex of bothfemales and males zQ175 animals at 4 months. GluN1 levels at 8 months were similar in the two groups of animals andalso between both sexes. Synaptophysin is a presynaptic protein involved in vesicle exocytosis. Surprisingly, we did notobserve any difference in synaptophysin levels either at 4 months or at 8 months. These results would suggest that thereare some early synaptic cortical changes in zQ175 HD mice that may affect corticostriatal pathway function.