Vasopressin (VP), a neuropeptide synthesized in hypothalamic magnocellular neurons is involved in a large number of different functions and mechanisms: control of body temperature, blood pressure, brain development, circadian rhythmicity, memory modulation, aggressive, and sexual behavior. Most of the studies on the age-related changes in VP levels in the paraventricular nucleus (PVN) reported the absence of any neuronal loss during normal aging in rodents and humans. On the contrary, other studies documented a decrease in the VP-neurons number during aging with an increase in the size of VP cells. Also in human neurodegenerative disease, like Alzheimer’s disease (AD) and Down syndrome (DS), in spite of a severe cholinergic deficit, VP neurons in PVN have been reported to exhibit either no significant loss or a significant decrease. The Ts65Dn mouse, bearing a partial triplication of chromosome 16, is the most common murine model for DS. These mice show severe deficits in learning and memory and decrease of some neural circuits, as the nitrinergic system of basal forebrain (3 months of age) and the cholinergic system (6–8 months of age). At these early stages the VP system in the PVN is not altered. In the present study, we have investigated changes in VP immunoreactivity in the PVN of Ts65Dn or wild type female mice at the age of 18 months. Mice were perfused with 4% paraformaldehyde, brains were dissected and frozen; coronal cryostatic sections were stained for vasopressin immunohistochemistry. Trisomic female mice showed a significant (p < 0.01) decrease of VP cell number in PVN compared to wild type female mice of the same age. Moreover, we have found in Ts65Dn female mice a statistically significant increase (p < 0.001) in cell size of PVN neurons. Therefore, this system, related to the control of autonomic control and osmoregulation, seems to be deeply affected in old mutant mice. Present data support those collected in human AD and DS patients showing alterations in osmoregulation and autonomic functions, and indicate the VP system of PVN as the major locus responsible of these changes.
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