Arcuate nucleus of the hypothalamus: Effects of age and sex

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Abstract
The arcuate nucleus of the hypothalamus (ARN) is involved in a variety of functions known to be sexually dimorphic and altered by aging. Although the effects of sex and age on the synaptic organization and neurochemistry of the ARN have been extensively analyzed, data regarding sex-related differences and age-induced effects on the total number of neurons and volume of the ARN in adult and aged male and female rats are controversial. To address this issue, we have quantitatively analyzed the ARN of male and female Wistar rats aged 6 and 24 months. The optical fractionator, the optical rotator, and the Principle of Cavalieri were used as the estimators of the total number of neurons, mean nuclear volume of ARN neurons, and volume of the ARN, respectively. In addition, a Golgi study was carried out to analyze the dendritic trees of its neurons. We found that in young adult rats, the volume of the ARN is 0.9 mm3 in males and 0.7 mm3 in females, whereas the total number of neurons is 100 x 10(3) in males and 86 x 10(3) in females. ARN neurons of males and females have identical mean nuclear volumes, which we estimated to be 300 microm3. No significant effects of age were found in these parameters, both in males and in females. In adult rats, no sex-related differences were detected in the number of dendritic segments and in the total dendritic length, but the dendritic branching density and the spine density were greater in females than in males. In aged rats there was a significant reduction in the number of dendritic segments, in the total dendritic length, and in the branching and spine densities that, although evident in both sexes, was more marked in females. Our results show that the total number of neurons and the volume of the ARN are sexually dimorphic in adult and aged rats and that neither of these parameters is altered by aging. Conversely, aging induces regressive changes in the dendritic arborizations of ARN neurons of males and females and abolishes the sexual dimorphic pattern of their organization.