Activation of Vasopressin Neurons in Aging and Alzheimer's Disease

The supraoptic (SON) and paraventricular nuclei (PVN) of the human hypothalamus are production sites of vasopressin (AVP) and oxytocin (OXT). Although the hypothalamus is affected in Alzheimer's disease (AD), previous work has not only shown that in these two nuclei no neurons are lost, neither during aging nor in AD, but that the number of AVP-expressing neurons and their nucleolar size had even increased with age. These observations indicated that the peptide synthesis of the AVP neurons was activated in the oldest age-groups. Recently published, qualitative observations, using the area of the Golgi Apparatus (GA) as a sensitive parameter for neurosecretory activity, confirmed the activation of SON and PVN neurons with age in human; however, in this report the neurons were not identified according to their neuropeptide content. In the present quantitative study we determined whether the AVP neurons were indeed activated as a result of the aging process in controls and AD patients. We applied a polyclonal antiserum directed against the medial cisternae of the GA on formalin-fixed, paraffin-embedded tissue sections taken from the dorsolateral SON (dl-SON) of 10 controls and 10 AD patients, and performed our measurements in this area that is known to be predominantly occupied (90–95%) by AVP neurons. In addition, the sparse OXT cells present in the area of study, were excluded from the measurements on the basis of alternative sections stained for OXT. In the dl-SON, the area occupied by the GA and the cellular profile area per patient were quantified by means of image analysis. The results show a significant increase in GA area with age in controls and in AD, demonstrating an activation of the AVP neurons in the dl-SON of the human hypothalamus in these two conditions. No changes were observed in the cellular profile areas with age, neither in the controls nor in AD, suggesting that the GA area is a much more sensitive parameter for monitoring activity changes in post-mortem material than neuronal size. It is proposed that this activation of AVP cells with age, which has been suggested to be a compensatory response to the age-related loss of AVP receptors in the kidney, might be the basis of the stability of these neurons in aging and AD.