Changes in brainstem serotonergic and dopaminergic cell populations in experimental and clinical Huntington's disease

The predominant motor symptom in Huntington's disease (HD) is chorea. The patho-anatomical basis for the chorea is not well known, but a link with the dopaminergic system has been suggested by post-mortem and clinical studies. Our previous work revealed an increased number of dopamine-containing cells in the substantia nigra and ventral tegmental area in a transgenic rat model of HD (tgHD). Since there were no changes in the total number of cells in those regions, we hypothesized that changes in cell phenotype were taking place. Here, we tested this hypothesis by studying the dorsal raphe nucleus (DRN), which houses dopaminergic and non-dopaminergic (mainly serotonergic) neurons in tgHD rat tissue and postmortem HD human tissue. We found an increased number of dopamine and reduced number of serotonin-containing cells in the DRN of tgHD rats. Similar findings in postmortem HD brain tissue indicate that these changes also occur in patients. Further investigations in the tgHD animal tissue revealed the presence of dopaminergic cell bodies in the B6 raphe region, while in control animals exclusively serotonin-containing cells were found. These data suggest the existence of phenotype changes in monoaminergic neurons in the DRN in HD and shed new light on the neurobiology of clinical neurological symptoms such as chorea and mood changes.

► More dopaminergic cells were found in the DRN of tgHD rats and HD patients. ► Serotonergic cell population was reduced in the DRN of tgHD rats and HD patients. ► We report an enhanced TH expression in the striatum of tgHD rats. ► Tissue levels of serotonin were reduced in the mPFC of tgHD rats. ► Our results suggest that neurotransmitter respecification takes place in HD.