Huntington’s Disease

Project 6: Age-dependent changes in different brain areas of mouse models of Huntington’s disease

Summary:

In this project we are investigating the BDNF signaling and related biomarkers in two mouse models of Huntington’s disease, including studies of 12- and 22- month-old YAC128 mice, as well as in 4-6 week-week-old of R6/2 mice. We will compare the changes of all the biomarkers in the striatum, cortex, and hippocampus in both male and female mice. These groups will be compared with the 12-month-old YAC128 mice which have been treated with curcumin for 2 months. This study is being conducted by Panchanan Maiti (below).

Project 7: Comparison of ovine- and bovine-sourced GM1 ganglioside for reducing cognitive and motordysfunction in rodent models of Huntington’s disease.

Summary:

GM1 gangliosides have been shown to be neuroprotective in various rodent models of Huntington’s disease. However, bovine-sourced GM1, which is obtained from a large number of cow brains, is very expensive. As an alternative, sheep raised with a ganglioside storage disorder produces four times as much GM1 as that obtained from bovine brains. The goal of this project is to determine whether ovine-sourced GM1 is as effective as bovine-source GM1 in treating the cognitive and motor dysfunction in the YAC 128 and R6/2 mouse models of HD. This project is being conducted by Melissa Resk (left below), Sindhuja Koneru (right below), and Ohanes Khacherian.

Project 8: Use of CRISPR-Cas9 gene-editing tool to reduce the amount of mutated huntingtin protein and ameliorate cognitive and motor deficits in a rodent model of Huntington's disease.

Summary:

Work in the FNI lab at CMU has indicated that altering the transcription of the gene related to Huntington’s disease using CRISPR-Cas9 can reduce the amount of mutated huntingtin protein and increase the survival of cultured cells from the YAC 128 mouse model of HD. We hope to replicate this finding by delivering this CRISPR-Cas9 tool into YAC 128 mice to see whether it can reduce the neuropathology and behavioral deÀ cits in this model of HD. This project is being conducted by Sindhuja Koneru (below).

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