Development of Hippocampus-Associated Cognitive Disfunction in Huntington's Disease Mouse Model
Huntington's disease is a hereditary, incurable neurodegenerative disease characterized by movement disorders – progressive choreic hyperkinesis, as well as cognitive and mental disturbances, including memory impairments, depression, panic attacks, obsessive compulsions, etc. According to literature data, mild cognitive impairments begin to appear even before the first motor symptoms. It is believed that the neurodegeneration of the cortex and striatum plays a major role in the development of cognitive dysfunction. At the same time, pathological changes in the hippocampus, which can also cause cognitive impairment, have been studied to a much lesser extent. In the present study, using electrophysiological experiments, morphofunctional analysis, and behavioral tests, we performed a comprehensive assessment of hippocampus-associated changes in a YAC128 transgenic mouse strain that model Huntington's disease. The revealed disturbances in the mechanisms of synaptic plasticity and changes in the morphology of synapses in the hippocampus in YAC128 mice are progressive and are observed earlier than disturbances in the coordination of movements. Thus, the results obtained support the hypothesis of the development of neurodegenerative changes in the hippocampus, which contribute to the cognitive dysfunction in Huntington's disease.