Vasopressin (VP) is a neuropeptide synthesized in hypothalamic magnocellular neurons and involved in a large number of different functions and mechanisms: control of body temperature, blood pressure, brain development, circadian rhythmicity, modulation of memory, aggressive and sexual behaviour. 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, others 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’ 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 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 control female mice at the age of 18 months. Mice were perfused with 4% paraformaldehyde, brains were dissected and frozen; finally, cryostatic sections were stained for vasopressin immunohistochemistry. Trisomic female mice showed a significant (p<0,01) decrease of VP cell number and an increase in cell size in PVN compared to wild type female mice of the same age. Therefore, this system, related to the control of autonomic control and osmoregulation, seems to be deeply affected in old mutant mice. Present data support therefore 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 responsible of these changes.
Vasopressinergic system and aging in the female Ts65Dn mouse, a murine model for Down syndrome
PANZICA, Giancarlo;GOTTI, STEFANO
2006-01-01
Abstract
Vasopressin (VP) is a neuropeptide synthesized in hypothalamic magnocellular neurons and involved in a large number of different functions and mechanisms: control of body temperature, blood pressure, brain development, circadian rhythmicity, modulation of memory, aggressive and sexual behaviour. 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, others 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’ 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 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 control female mice at the age of 18 months. Mice were perfused with 4% paraformaldehyde, brains were dissected and frozen; finally, cryostatic sections were stained for vasopressin immunohistochemistry. Trisomic female mice showed a significant (p<0,01) decrease of VP cell number and an increase in cell size in PVN compared to wild type female mice of the same age. Therefore, this system, related to the control of autonomic control and osmoregulation, seems to be deeply affected in old mutant mice. Present data support therefore 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 responsible of these changes.
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