Mitigation of hippocampal dysfunction and cognitive deficits in early-symptomatic YAC128 transgenic mice for Huntington’s disease

Huntington's disease is a devastating neurodegenerative disorder affecting between three and 10 individuals per 100,000 in the Western world. It is caused by a mutation in the huntingtin gene, which results in the accumulation of mutated huntingtin protein in the brain and the eventual degeneration of certain types of brain cells. The disease is primarily characterized by the onset of motor deficits; this develops when the striatum region deep within the brain begins to degenerate. However, Huntington’s disease patients commonly show cognitive impairments decades before the onset of the motor symptoms. The hippocampus is a brain region known to be involved both in cognitive (i.e. learning and memory) and emotional (i.e. depression) processes.

Dr. Joana Gil-Mohapel is investigating whether the hippocampus is involved in the early cognitive impairments in Huntington’s disease. She is working with a mouse model of Huntington’s disease, which closely mimics the human condition. These mice demonstrate profound structural and functional deficits in this region; significantly, as seen in Huntington’s disease patients, these deficits can be detected when the animals are still in an early-symptomatic stage, before the onset of motor symptoms. Therefore, the goal of the present research is to gain a better understanding of how this structure is affected in this mouse model.

Dr. Gil-Mohapel will investigate whether relevant cellular pathways are altered in this brain region and whether therapies aimed at promoting hippocampal function can reverse these deficits and be of therapeutic value for Huntington’s disease. She hopes her research will help elucidate novel targets for the mitigation of the cognitive deficits characteristic of early-stage Huntington’s disease patients.