Aging Alters the Rhythmic Expression of Vasoactive Intestinal Polypeptide mRNA But Not Arginine Vasopressin mRNA in the Suprachiasmatic Nuclei of Female Rats

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.

Suppression of Vasoactive Intestinal Polypeptide in the Suprachiasmatic Nucleus Leads to Aging-Like Alterations in cAMP Rhythms and Activation of Gonadotropin-Releasing Hormone Neurons

“…Symbols indicate levels of significance between time points (*p Ͻ 0.05; **p Ͻ 0.01; ***p Ͻ 0.001) and between treatments ( ## p Ͻ 0.01; ### p Ͻ 0.001). ( Krajnak et al, 1998a), at the same age we observed the disappearance in cAMP rhythms in the current study. VIP dynamics are sexually dimorphic and play essential roles in cyclic reproductive function in females.…”

“…Our findings confirm and extend the previous study by Chappell et al (2000) who showed that cAMP levels display a diurnal rhythm in the AVPV. It is particularly intriguing that the disappearance of the cAMP rhythms occur at the same age as previously reported alterations in VIP rhythms in the SCN and in the activation of GnRH neurons, which is required for LH surges to occur (Lloyd et al, 1994;Krajnak et al, 1998aKrajnak et al, , 2001Le et al, 2001;Legan and Tsai, 2003). Therefore, we explored whether these three neurochemicals (VIP, cAMP, and GnRH) are functionally linked.…”

“…Interestingly, Chappell et al (2000) reported that cAMP levels in the anteroventral periven-tricular nucleus (AVPV) exhibit a diurnal rhythm that is markedly analogous to the rhythm of VIP. Third, aging affects the rhythm of VIP in the SCN (Krajnak et al, 1998a), and suppression of this rhythm in young rats leads to delayed and attenuated LH surges that are strikingly similar to those observed in middleaged (MA) female rats (Harney et al, 1996;van der Beek et al, 1999).…”

Aging in the circadian system: Considerations for health, disease prevention and longevity

“…Two SCN peptides, VIP and AVP, have long been implicated in stimulation of the reproductive axis. VIP mRNA but not AVP mRNA becomes arrhythmic in the SCN of middle-aged female hamsters (Krajnak et al, 1998), and suppression of SCN VIP in young female hamsters results in accelerated deficits in GnRH activation and an LH surge that mimic that of an aged population (Gerhold et al, 2005;Harney et al, 1996). Together, these findings suggest that age-related deficits in the neuroendocrine mechanisms mediating ovulation may result from loss of function at the level of the SCN.…”

Age-related changes in neurochemical components and retinal projections of rat intergeniculate leaflet

“…Moreover, SCN have a reduced expression of two major neurochemical constituents, vasoactive intestinal polypeptide (Chee et al 1988;Krajnak et al 1998), and vasopressin (Roozendaal et al 1987;Cayetanot et al 2005), which accounts to a weakening of SCN interconnections, therefore affecting the circadian clock functionality (Engelberth et al 2013). Current data, however, are focused solely on the aging effects on SCN, which brings a limitation to understand the whole process of aging in CTS (Yamazaki et al 2002;Davidson et al 2008).…”