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H04 Gene Expression Changes In Emotion And Metabolism Regulating Neuropeptide Systems In The Hypothalamus In Clinical Huntington Disease
  1. S Gabery1,
  2. R Soylu-Kucharz1,
  3. C McLean2,
  4. D Kirik3,
  5. G Halliday4,
  6. Å Petersén1
  1. 1Translational Neuroendocrine Research Unit, Department of Experimental Medical Science, Lund University, Sweden
  2. 2Department of Pathology, Alfred Hospital, Melbourne, Victoria, Australia
  3. 3B. R. A. I. N. S. Unit, Department of Experimental Medical Science. Lund University, Sweden
  4. 4Neuroscience Research Australia and the University of New South Wales, Sydney, Australia

Abstract

Background The homeostatic control of emotions and metabolism is disturbed in Huntington disease (HD). We have recently shown that specific neuropeptide populations in the hypothalamus are affected in HD patients. Transcriptional dysregulation is well known to occur in HD and it has been reported also in the hypothalamus of transgenic HD mice. Less is known about the extent of transcriptional dysregulation in the different hypothalamic nuclei in clinical HD.

Aim To investigate whether there are changes in gene expression levels of emotion and metabolism regulating factors in key hypothalamic circuitries in human post mortem tissues from individuals affected with HD.

Methods/techniques We have dissected frozen tissue from the paraventricular nucleus, the ventromedial nucleus, the lateral hypothalamus and the supraoptic nucleus of the hypothalamus from 4 HD cases and 4 sex-and age-matched controls. The tissue was then processed for quantitative real time PCR.

Results/outcome The RNA integrity value was found to be above 7 for all samples. Our results show reduced mRNA expression levels of orexin (hypocretin) in the lateral hypothalamus as well as of dopamine receptor D2 expression in HD. We have also detected reduced expression of brain-derived neurotrophic factor (BDNF) in the ventromedial hypothalamus in HD.

Conclusions These results show significant and specific alterations in gene expression in key hypothalamic nuclei involved in the regulation of emotions and metabolism. Transcriptional alterations in this region may be important for the development of the early non-motor symptoms and signs in HD, and may provide potential targets for therapeutic interventions.

KeyWords
  • Hypothalamus
  • gene expression
  • BDNF
  • orexin

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