Age-related decline in hypocretin (orexin) receptor 2 messenger RNA levels in the mouse brain.
The hypocretin (Hcrt; also known as orexin) system has been implicated in arousal state regulation and energy metabolism. We hypothesize that age-related sleep problems can result from dysfunction of this system and thus measured messenger RNA (mRNA) levels of preprohcrt in the hypothalamus, and hcrt receptor 1 (hcrtr1) and hcrt receptor 2 (hcrtr2) in eight brain regions of 3, 12, 18 and 24 months old C57BL/6 mice. Expression of preprohcrt and the colocalized prodynorphin did not change with age. Whereas an age-related change in hcrtr1 mRNA expression was observed only in the hippocampus, hcrtr2 mRNA levels declined in the hippocampus, thalamus, pons, and medulla; these reductions ranged from 33 to 44%. Declining trends (P < 0.1) in hcrtr2 mRNA levels were also observed in the cortex, basal forebrain and hypothalamus. These results are consistent with the hypothesis that an age-related deterioration occurs in the Hcrt system that may contribute to age-related sleep disorders.
Terao
Akira
A
Molecular Neurobiology Laboratory, SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA.
Apte-Deshpande
Anjali
A
Morairty
Stephen
S
Freund
Yvonne R
YR
Kilduff
Thomas S
TS
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000254:growth & development*; D001923:Brain Chemistry / Q000235:genetics / Q000502:physiology*; D004745:Enkephalins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D064446:Orexin Receptors; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000096:biosynthesis* / Q000235:genetics
D004745:Enkephalins; C578628:Hcrtr2 protein, mouse; D064446:Orexin Receptors; D011498:Protein Precursors; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; C033660:preproenkephalin