B07 Metabolic characteristics of primary neuron cultures from bachd rats compared to induced lesion models

Abstract

Background The BACHD rat is by now a well characterized animal model of Huntington’s disease (HD), presenting several disease relevant symptoms and pathologies. The BACHD rat represents one of the few animal models that overexpresses the full length human mutant huntingtin (mHTT) and is thus of great value for HD research. Aims The aim of this study was to compare the metabolic properties of primary striatal, hypothalamic and cortical neurons of BACHD rats with the l-glutamate or MPP+ induced rat striatal lesion models to establish BACHD primary cells as valuable in vitro HD model. Methods BACHD rat pups, as well as wildtype pups, were dissected at embryonic day 19 and primary neurons of the striatum, hypothalamus and cortex were cultivated. Cells were analyzed after 1, 7 and 14 days in vitro. For the lesion models, primary striatal embryonic day 19 rat neurons were cultivated for 15 days and lesioned with l-glutamate or MPP+ for 24 hours. All samples were analyzed with the MTT- and LDH-assay. Results Our data show that primary neurons of embryonic BACHD rats show a significantly decreased metabolic activity in the striatum and hypothalamus. These results are comparable with data obtained by l-glutamate or MTT+ lesions in primary striatal neurons of wildtype rats. Conclusions We conclude that the BACHD rat model is a valuable tool for the in vitro evaluation of HD-related metabolic properties.