Aging selectively suppresses vasoactive intestinal peptide messenger RNA expression in the suprachiasmatic nucleus of the Syrian hamster

Aging leads to many changes in the expression of circadian rhythms, includi ng reduced amplitude, altered relationship to the environmental illuminatio n cycle, and reduced sensitivity to phase resetting signals. Neuropeptide s ynthesizing neurons in the suprachiasmatic nucleus (SCN), the principal cir cadian pacemaker in mammals, play a role in regulating pacemaker function a nd in coupling the pacemaker to overt circadian rhythms. Aging may alter th e activity of neuropeptide neurons in the SCN, which could be reflected in changes in mRNA expression. Therefore, this study investigated whether agin g alters the level or rhythm of expression of neuropeptide mRNAs in the SCN of male Syrian hamsters, a well established model for the study of age-rel ated changes in circadian rhythms. Three age groups of hamsters (young [3-5 months old], middle-aged [12-15 months old] and old [19-22 months old] wer e sacrificed at five times of day. Their brains were dissected and sections through the suprachiasmatic nucleus were prepared and used for in situ hyb ridization for mRNAs for vasoactive intestinal peptide (VIP), arginine vaso pressin (AVP) and somatostatin (SS). Aging selectively decreased the SCN ex pression of VIP mRNA without affecting AVP mRNA or SS mRNA. Also, only AVP mRNA expression exhibited a robust 24-h rhythm, in contrast to previous fin dings in other species that VIP mRNA and SS mRNA, as well as AVP mRNA, exhi bit 24-h rhythms in the SCN. The present findings suggest that age-related reductions in VIP mRNA expression may contribute to the alterations in entr ainment and attenuated sensitivity to phase resetting signals that are char acteristic of aging. Furthermore, the results demonstrate that neuropeptide gene expression in the SCN is differentially regulated by aging and varies among species. (C) 2001 Elsevier Science B.V. All rights reserved.