Paraventricular nucleus neuropeptide expression in Huntington's disease patients

Brain Pathol. 2012 Sep;22(5):654-61. doi: 10.1111/j.1750-3639.2012.00565.x. Epub 2012 Feb 16.

Abstract

Neuroendocrine, metabolic and autonomic nervous system dysfunctions are prevalent among patients with Huntington's disease (HD) and may underlie symptoms such as depression, weight loss and autonomic failure. Using post-mortem paraffin-embedded tissue, we assessed the integrity of the major neuropeptide populations in the paraventricular nucleus (PVN)-the hypothalamic neuroendocrine and autonomic integration center-in HD patients. The number corticotropin-releasing hormone, cocaine- and amphetamine-regulated transcript, arginine vasopressin and oxytocin immunoreactive (ir) neurons did not differ between HD patients and control subjects. However, the significant positive correlation between arginine vasopressin and oxytocin ir neurons in control subjects (P = 0.036) was absent in patients. Corticotropin-releasing hormone mRNA levels were 68% higher in HD patients (P = 0.046). Thyrotropin-releasing hormone mRNA levels did not differ between HD patients and control subjects, although a negative correlation with disease duration was present in the former (P = 0.036). These findings indicate that the PVN is largely unaffected in HD patients. However, our findings suggest that hypothalamic-pituitary-thyroid axis activity may alter during the course of the disease and that autonomic nervous system dysfunction might partly arise from an imbalance between arginine vasopressin and oxytocin neurons in the PVN.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Arginine Vasopressin / genetics
  • Arginine Vasopressin / metabolism
  • Corticotropin-Releasing Hormone / genetics
  • Corticotropin-Releasing Hormone / metabolism
  • Female
  • Humans
  • Huntington Disease / pathology*
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / metabolism
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Oxytocin / genetics
  • Oxytocin / metabolism
  • Paraventricular Hypothalamic Nucleus / metabolism*
  • Paraventricular Hypothalamic Nucleus / pathology
  • RNA, Messenger / metabolism
  • Statistics, Nonparametric

Substances

  • Nerve Tissue Proteins
  • Neuropeptides
  • RNA, Messenger
  • cocaine- and amphetamine-regulated transcript protein
  • Arginine Vasopressin
  • Oxytocin
  • Corticotropin-Releasing Hormone