Changes in hypothalamic corticotropin-releasing hormone, neuropeptide Y, and proopiomelanocortin gene expression during chronic rapid eye movement sleep deprivation of rats.
Chronic rapid eye movement (paradoxical) sleep deprivation (REM-SD) of rats leads to two conspicuous pathologies: hyperphagia coincident with body weight loss, prompted by elevated metabolism. Our goals were to test the hypotheses that 1) as a stressor, REM-SD would increase CRH gene expression in the hypothalamus and that 2) to account for hyperphagia, hypothalamic gene expression of the orexigen neuropeptide Y (NPY) would increase, but expression of the anorexigen proopiomelanocortin (POMC) would decrease. Enforcement of REM-SD of adult male rats for 20 d with the platform (flowerpot) method led to progressive hyperphagia, increasing to approximately 300% of baseline; body weight steadily declined by approximately 25%. Consistent with changes in food intake patterns, NPY expression rapidly increased in the hypothalamic arcuate nucleus by d 5 of REM-SD, peaking at d 20; by contrast, POMC expression decreased progressively during REM-SD. CRH expression was increased by d 5, both in mRNA and ability to detect neuronal perikaryal staining in paraventricular nucleus with immunocytochemistry, and it remained elevated thereafter with modest declines. Taken together, these data indicate that changes in hypothalamic neuropeptides regulating food intake are altered in a manner consistent with the hyperphagia seen with REM-SD. Changes in CRH, although indicative of REM-SD as a stressor, suggest that the anorexigenic actions of CRH are ineffective (or disabled). Furthermore, changes in NPY and POMC agree with current models of food intake behavior, but they are opposite to their acute effects on peripheral energy metabolism and thermogenesis.
Koban
Michael
M
Department of Anatomy and Neurobiology, Richard N. Dixon Science Research Building Department of Biology, Morgan State University, Baltimore, Maryland 21251, USA.
Le
Wei Wei
WW
Hoffman
Gloria E
GE
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D007031:Hypothalamus / Q000503:physiopathology*; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics*; D011333:Pro-Opiomelanocortin / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012892:Sleep Deprivation / Q000235:genetics / Q000503:physiopathology*; D012895:Sleep, REM / Q000502:physiology*; D015431:Weight Loss
D009478:Neuropeptide Y; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone