The neurosecretory system is hypertrophied in senescence-accelerated mice
D. Crespo, M. Megias, C. Fernandez-Viadero, L. Alonso, R. Verduga
Biogerontology. Faculty of Medicine. University of Cantabria. 39011-Santander. Spain
The neurosecretory system (NSS) of the hypothalamus acts as a pivotal
area that regulates important endocrine functions. The NSS has been
studied from different points of view and its anatomical, cellular, and
electrophysiological features have become important areas of research.
Furthermore, the NSS has been related to some ageing processes in which
its activity could play an important role in regulating the
overall-ageing process. The NSS is formed by the paraventricular and
supraoptic nuclei whose neurons synthesize the neurohormones oxytocin
and arginine-vasopressin. These hormones are transported through the
neurosecretory tract to the neurohypophysis where they are released
into the circulatory system. In addition, other scattered
neurosecretory neurons are located throughout the anterior hypothalamic
area; they rarely group and form variable and poorly distinctive nuclei
called "accessory nuclei".
The senescence-accelerated mouse (SAM) is a murine model of rapid
ageing once adulthood is reached. There are two main SAM strains with
respect to the ageing span, the prone (SAM-P) and the retarded (SAM-R).
The SAM-P has an average life span of 12 months while SAM-R reaches up
to 17 months. This animal model has been widely used to analyze
morphological, behavioural, and molecular processes associated with
ageing. The SAM-P8 has been reported to display senile amyloidosis,
which has been defined as a group of diverse conditions characterized
by the extracellular accumulation of fine soluble amyloid fibrils, for
which age is the only risk factor. This deposition affects all organs,
except bone and brain parenchyma. Furthermore, age-related spongy
degeneration, astrogliosis, microglial reaction, and blood-brain
barrier dysfunction have been observed in some brain areas of these
mice. Memory and learning problems related to these neural alterations
have also been reported. In addition, our previous results in these
mice demonstrated differences in the circadian rhythm of SAM-P8 and
SAM-R1, although there were no differences in the number of
arginine-vasopressin cells in the suprachiasmatic nuclei. Now, we
extend the characterization of the hypothalamus of this strain and
describe the presence of a constant well-developed arrangement of
neurosecretory neurons which was located bilaterally in close proximity
to the third ventricle wall and formed the mouse accessory cells
(MAC).
For this study we used SAM mice kindly provided by T. Takeda (Kyoto
University), and bred in our animal facilities. We used SAM-R1 and
SAM-P8 of both sexes and three age groups: 5-month-old, 10-month-old
and, 14-month-old groups (5 animals for each strain and sex). We also
used other set of mice of both sexes of the Swiss, AKR and C57BL/6iv
strains respectively.
The morphology and cellular features of the MAC were similar in young,
adult and aged SAM, and in males and females. Unbiased stereological
analysis revealed that the MAC contained an average of 197 (SD=18)
neurons, most (87%) synthesize arginine-vasopressin, and a few (13%)
produce oxytocin. The DiI tracer revealed that these neurons project
into the median eminence. The consistent presence of the MAC, together
with the fact that it was poorly represented in the other mouse strains
used (AKR, Swiss, C57BL/6iv), suggests that the SAM hypothalamus could
present greater neurohormone synthesis increasing the deleterious
effects of accelerated ageing in this strain.
Key words:
ageing, neurohormones, senescence-accelerated mouse, hypothalamus
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