Abstract

Huntington's disease (HD) is a neurodegenerative disorder characterised by progressive cognitive impairments and chorea. The latter has been linked to an increased dopaminergic neurotransmission in the striatum. Treatment with dopamine (DA) antagonist or DA depleting drugs can reduce chorea. However, the origin of this hyperdopaminergic status remains unknown. Tracing studies have shown that dopaminergic input to the striatum comes from the substantia nigra pars compacta (SNc), ventral tegmental area, and a specific cell population of the dorsal raphe nucleus (DRN). Using Immunohistochemistry, we tested the hypothesis that elevated striatal DA level is related to alterations in these regions in a transgenic rat model of HD (tgHD) and in the DRN of human HD specimens. We found that the origin of increased levels of DA in the striatum might be linked to an increase in the number of dopaminergic cells in the ventral tegmental area, SNc and the DRN of tgHD rats. In addition, we observed increased number of dopaminergic and reduced number of serotonergic cells in the DRN of tgHD rats and HD patients. We suggest that the underling mechanism for this hyperdopaminergic status in HD can be due to a change in phenotype of the non-dopaminergic cells, like serotonergic cells into dopaminergic cells.