A23 Changes in key hypothalamic neuropeptide populations in Huntington's Disease revealed by neuropathological analyses

Background The homeostatic control of emotions and metabolism is disturbed early in Huntington9s disease (HD), which may be due to changes in hypothalamic function. Previous studies have identified a loss of orexin (hypocretin) neurons in the lateral hypothalamus in HD patients. There has been only limited assessment of other hypothalamic regions in HD. Aims The aim of the study was to assess the neuropeptide expressing hypothalamic neurons known to regulate metabolism and emotion in HD patients compared with healthy controls. Methods Hypothalamic serial sections from HD (n=6) and controls (n=4) cases were processed for cresyl violet, Luxol fast blue and immunohistochemistry. Quantification of total cell numbers was performed using unbiased stereology. Results Substantial differences exist in peptide expression of different neuronal populations in HD hypothalamus compared with controls. In addition to loss of orexin expressing neurons, both oxytocin and vasopressin expressing neurons were decreased. The number of cocaine and amphetamine regulated transcript (CART) expressing neurons was increased. The increased expression of CART in the hypothalamus is consistent with a previous study showing increased CART levels in CSF from HD patients. There was no difference in the numbers of neuropeptide Y expressing neurons. Conclusions These results show significant and specific alterations in the peptide expression of hypothalamic neurons known to regulate metabolism and emotion. These changes may be important for the development of the psychiatric symptoms and metabolic disturbances characterising HD, and may provide potential targets for therapeutic interventions.