vasoactive-intestinal-peptide and Sleep-Wake-Disorders

To study whether sleep and circadian rhythm disturbances in patients with Huntington's disease (HD) arise from dysfunction of the body's master clock, the hypothalamic suprachiasmatic nucleus.. Postmortem cohort study.. Eight patients with HD and eight control subjects matched for sex, age, clock time and month of death, postmortem delay, and fixation time of paraffin-embedded hypothalamic tissue.. Using postmortem paraffin-embedded tissue, we assessed the functional integrity of the suprachiasmatic nucleus in patients with HD and control subjects by determining the expression of two major regulatory neuropeptides, vasoactive intestinal polypeptide and arginine vasopressin. Additionally, we studied melatonin 1 and 2 receptor expression. Compared with control subjects, the suprachiasmatic nucleus contained 85% fewer neurons immunoreactive for vasoactive intestinal polypeptide and 33% fewer neurons for arginine vasopressin in patients with HD (P = 0.002 and P = 0.027). The total amount of vasoactive intestinal polypeptide and arginine vasopressin messenger RNA was unchanged. No change was observed in the number of melatonin 1 or 2 receptor immunoreactive neurons.. These findings indicate posttranscriptional neuropeptide changes in the suprachiasmatic nucleus of patients with HD, and suggest that sleep and circadian rhythm disorders in these patients may at least partly arise from suprachiasmatic nucleus dysfunction.

Topics: Arginine Vasopressin; Chronobiology Disorders; Circadian Rhythm; Cohort Studies; Female; Humans; Huntington Disease; Hypothalamus; In Situ Hybridization; Male; Neuropeptides; Sleep Wake Disorders; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide

The neurological complications associated with infection by the AIDS virus, HIV, occurs at an early stage of the disease and often indicate a poor prognosis. A dementia, known as AIDS Dementia Complex, is the most common feature observed, and is found in a majority of patients. The effects of gp120, the external protein envelope of HIV, on cerebral glucose utilization were studied in rats. Intracerebroventricular injection of gp120 significantly reduced glucose utilization in the lateral habenula and the suprachiasmatic nucleus, two regions rich in receptors for Vasoactive Intestinal Peptide (VIP) and the whole brain metabolism showed a significant decrease. The findings suggest that gp120 may alter neuronal function, thereby contributing to sequelae of HIV infection of the brain, and that attachment of HIV particles may involve, for a part, VIP receptors.

Topics: Acquired Immunodeficiency Syndrome; Animals; Brain; Dose-Response Relationship, Drug; Glucose; HIV Envelope Protein gp120; HIV-1; Male; Rats; Rats, Inbred Strains; Sleep Wake Disorders; Vasoactive Intestinal Peptide