Nerve growth factor restores the expression of vasopressin and vasoactive intestinal polypeptide in the suprachiasmatic nucleus of aged rats

Aging leads to a decrease in the number of neurons expressing vasopressin (VP) and vasoactive intestinal polypeptide (VIP) in the suprachiasmatic nucleus (SCN) of the rat. Similar results were observed following prolonged alcohol consumption and withdrawal. In the latter circumstances, the administration of nerve growth factor (NGF) restored the synthesis and expression of those neuropeptides despite the absence of TrkA receptors in SCN neurons. Thus, we decided to test whether the administration of NGF would improve the expression of neuropeptides in the SCN of aged rats. For this purpose, NGF was delivered intraventricularly to aged rats over a period of 14 days. The somatic volume and the total number of VP- and VIP-immunostained SCN neurons were estimated by applying stereological methods. No age-related variations were found regarding the volume of the neuronal cell bodies. Yet, a striking reduction in the number of VP- and VIP-immunoreactive neurons was detected in aged animals and found to be completely retrieved by NGF. This finding shows that exogenous NGF administered to aged rats restores the neurochemical phenotype of the SCN. This might occur either through direct signaling of SCN neurons via p75NTR or through enhancement of the cholinergic input to the SCN.