The neurosecretory system of the senescence-accelerated mouse : a model of cognitive decline

Introduction: the senescence-accelerated mouse (SAM) is a murine model of rapid ageing once adulthood has been reached and there is a concomitant cognitive decline. The neurosecretory system of the hypothalamus is composed of the supraoptic and paraventricular nuclei, and their neurons synthesize the hormones oxytocin and vasopressin. A feature of the SAM is the presence of a well developed nucleus that does not appear in other mice strains, the accessory nucleus. The increase in neurosecretory hormone levels could play a role in the processes of ageing and cognitive decline. Material and methods: we used male and female mice of the two strains of SAM: ageing prone SAM-P8 (average life expectancy 12 months) and retarded SAM-R1 (average life expectancy 17 months). To compare our observations, we used several mice of the Swiss and AKR/J strains. After perfusion, several techniques were employed to analyse the hypothalamus of these mice; thionin, immunocytochemistry (oxytocin and vasopressin) and DiI to observe hypothalamic projections. The quantitative analysis was performed by a stereology approach. Results: the most interesting result observed was the presence of the accessory nucleus in SAM mice. This nucleus consists of an arrangement of some 200 neurons. Most of these neurons were vasopressinergic and some (13%) were oxytocinergic. Conclusions: the results obtained in this strain of accelerated senescence are in agreement with those reported in the aged human brain, in which there is an increase in the synthesis of these neurohormones, both in normal and some neuropathological conditions.