Arginine‐vasopressin and vasointestinal polypeptide rhythms in the suprachiasmatic nucleus of the mouse lemur reveal aging‐related alterations of circadian pacemaker neurons in a non‐human primate

Abstract

The suprachiasmatic nucleus (SCN) of the hypothalamus, the mammalian circadian pacemaker, is entrained by external cues and especially by photic information. Light is transmitted primarily via the retinohypothalamic tract, which terminates in the ventral part (or core) of the SCN, where vasoactive intestinal polypeptide (VIP)-containing neurons are located. VIP cells are mainly intrinsic and project to the dorsal part (or shell) of the SCN, where neurons containing arginine-vasopressin (AVP) reside. As aging leads to marked changes in the expression of circadian rhythms, we examined in primates whether age-related decay in biological rhythmicity is associated with changes in the oscillation of peptide expression in SCN neurons. We used double immunohistochemistry and quantitative analysis in the SCN of mouse lemurs, which provide a unique model of aging in non-human primates. In adult animals, VIP-positive and AVP-positive SCN neurons exhibited daily rhythms of their number and immunostaining intensity: AVP immunoreactivity peaked during the second part of the day, and VIP peaked during the night. In aged mouse lemurs, the peaks of AVP and VIP immunopositivity were significantly shifted, so that AVP was most intense at the beginning of the night, whereas VIP peaked at the beginning of daytime. The results show that the circadian rhythm of neuropeptides in the SCN is modified by aging in primates, with a differential regulation of the two main peptidergic cell populations. These changes may affect the ability of the SCN to transmit rhythmic information to other neural target sites, and thereby to modify the expression of some biological rhythms.

Circadian disruption and SCN control of energy metabolism

“…The flattening of the daily rhythm in vasopressin abundance was already observed in subjects >50 years of age (160). Similar decreases in the expression of vasopressin in the SCN were also noted in aging experimental animals (161–163). Harper et al (164) very elegantly demonstrated that the loss of SCN vasopressin-expressing neurons in the human postmortem brain significantly correlated with an increased deterioration of activity rhythms before death.…”

The aging clock: circadian rhythms and later life

“…14, 64, 106, 107, and Figure 3). A similar reduction in AVP and VIP expression has been observed in aged rodents (108,109), whereas in mouse lemurs, a nonhuman primate, the peak of rhythmic AVP and VIP expression in the SCN is shifted, not suppressed, in aged animals compared with younger adults (110).…”

Aging of Non-Visual Spectral Sensitivity to Light in Humans: Compensatory Mechanisms?

“…AVP (arginine vasopressine neurons in the dorsomedial region of the SCN) and VIP (vasoactive intestinal polypeptide, in the ventrolatreal region of SNC), constitute the main output pathway of the SCN to the rest of the brain. Several animal and human studies reported an age-related shift [70] and decrease in the rhythmic synthesis, oscillation and release of these neuropeptides [25], [71] along with a decrease in the number of AVP-expressing neurons in the SCN [72]. Post-mortem analyzed of human brains, also show a flattened diurnal oscillation of AVP expression in older subjects compared to young [73].…”