D. Crespo, M. Megias, C. Fernandez-Viadero, L. Alonso, R. Verduga

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.

Keywords (Optional): 
senescence-accelerated mouse