Abstract

Our laboratory has shown that the ability of the suprachiasmatic nuclei (SCN) to regulate a number of rhythmic processes may be compromised by the time females reach middle age. Therefore, we examined the effects of aging on the rhythmic expression of two neuropeptides synthesized in the SCN, vasoactive intestinal polypeptide (VIP) and arginine vasopressin (AVP), using in situ hybridization. Because both VIP and AVP are outputs of the SCN, we hypothesized that age-related changes in rhythmicity are associated with alterations in the patterns of expression of these peptides. We found that VIP mRNA levels exhibited a 24 hr rhythm in young females, but by the time animals were middle-aged, this rhythm was gone. The attenuation of rhythmicity was associated with a decline in the level of mRNA per cell and in the number of cells in the SCN producing detectable VIP mRNA. AVP mRNA also showed a robust 24 hr rhythm in young females. However, in contrast to VIP, the AVP rhythm was not altered in the aging animals. The amount of mRNA per cell and the number of cells expressing AVP mRNA also was not affected with age. Based on these results we conclude that (1) various components of the SCN are differentially affected by aging; and (2) age-related changes in various rhythms may be attributable to changes in the ability of the SCN to transmit timing information to target sites. This may explain why the deterioration of various rhythmic processes occurs at different rates and at different times during the aging process.

Highlights

  • All organisms exhibit 24 hr rhythms in numerous physiological and behavioral processes. These rhythms are entrained to the light /dark (LD) cycle by a circadian pacemaker located in the suprachiasmatic nuclei (SC N) (Meijer and Rietveld, 1989)

  • Further analyses showed that vasoactive intestinal polypeptide (VIP) mRNA levels per cell were lower in middle-aged and old than in young females ( p Ͻ 0.05)

  • The purpose of this study was to examine the effects of aging on two major peptides synthesized within the SC N, V I P and arginine vasopressin (AVP), to determine whether the rhythmic expression of their mRNAs was altered

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Summary

Introduction

All organisms exhibit 24 hr rhythms in numerous physiological and behavioral processes. Both VIP and AVP neurons relay circadian information to the basal forebrain and various hypothalamic and thalamic nuclei (Watts and Swanson, 1987) These projections regulate rhythms of gonadotropin-releasing hormone (GnRH) release (Cheesman et al, 1977; Osland et al, 1977; van der Beek et al, 1995; Harney et al, 1996; Palm et al, 1997) and glucocorticoid release (Scarbrough et al, 1996; Buijs, 1997) and activity (Pickard and Turek, 1983; Sollars and Pickard, 1995; Murphy et al, 1997). If only some of the components of the clock are affected with age, we might observe differential effects on V I P compared with AV P

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