Disorders of the Nervous System
Author: Luisina Castellari | email: luisinacastellari@hotmail.com
Luisina Castellari 1°, Julieta Saba 2°, Federico López Couselo 2°, Maria Veronica Baez 1°, Carla Mariana Caruso 2°
1° Instituto de Biología Celular y Neurociencias Prof. E. De Robertis (IBCN, CONICET-UBA), Buenos Aires, Argentina.
2° Instituto de Investigaciones Biomédicas (INBIOMED), UBA-CONICET, Paraguay 2155, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina
Huntingtons disease (HD) is a predominantly heritable neurodegenerative disorder caused by a mutation in the huntingtin gene, which leads to expansion of the CAG repeat within exon 1 of the protein. Synaptic signaling alterations underlie the behavioral and neuropathological changes observed during HD. In particular, there is increased cortical excitability in presymptomatic patients. Dysregulation of glutamatergic signaling is known to play an important role in this disease and may contribute to early synaptic dysfunction observed in HD. In this work, using a zQ175 knock-in mouse model, we characterized NMDA receptor levels in the cortex and striatum of Huntington (zQ175) and wild-type (WT) mice at 4 and 8 months of age. Preliminary results suggest that GluN1 levels are increased in the cerebral cortex of both females and males zQ175 animals at 4 months. GluN1 levels at 8 months were similar in the two groups of animals and also between both sexes. Synaptophysin is a presynaptic protein involved in vesicle exocytosis. Surprisingly, we did not observe any difference in synaptophysin levels either at 4 months or at 8 months. These results would suggest that there are some early synaptic cortical changes in zQ175 HD mice that may affect corticostriatal pathway function.