Effects of Intrahypothalamic Administration of microRNA Inhibitors and Mimetics on Blood Plasma Biomarkers in the Rat Aging.

The effect of let-7a-5p, miR-9a-3p, miR-132-3p, miR-218a-5p microRNA inhibitors and mimetics, when administered into the dorsomedial nucleus of the hypothalamus (DMN), on the markers of age-related changes in blood plasma in 3-month-old and 24-month-old male rats was studied. In the 24-month-old control rats, the content of C-reactive protein (CRP) increased, and the level of myoglobin decreased compared to the 3-month-old animals. After te administration of miRNA inhibitors, the level of CRP significantly increased, and the content of myoglobin decreased, and after the administration of miRNA mimetics, opposite changes were observed. We found no significant differences in the content of somatotropic hormone and testosterone between the control and experimental groups, as well as between the 3-month-old and 24-month-old animals.

[Age-related changes in AKT and mTOR expression in mediobasal hypothalamus neurons with aging.]

The hypothalamus is a regulatory center that controls homeostasis, reproduction, circadian rhythms, and the endocrine system. It is also involved in the regulation of aging. Expression of protein kinase B (AKT), the mammalian target of rapamycin (mTOR), and phosphorylated forms of AKT (pAKT) and mTOR (pmTOR) was studied by Western blotting in 3-, 12-, and 24-month-old male rats in the arcuate (ARN), dorsomedial (DMN) and ventromedial (VMN) nuclei of the hypothalamus. The results showed that the components of AKT/mTOR signaling change differently in the mediobasal hypothalamic nuclei of rats with age. The expression of AKT and pAKT decreased in the ARN, DMN, and VMN with aging; the expression of mTOR and pmTOR increased in the ARN, but decreased in the DMN and VMN in aged rats. The results obtained can serve as a basis for future studies of the mechanisms of age-related diseases and their pharmacological treatment.

Expression of GAD65/67 and VGLUT2 in Mediobasal Nuclei of Rat Hypothalamus during Aging.

The expression of glutamate decarboxylase GAD65/67, an enzyme of GABA synthesis, and vesicular glutamate transporter 2 (VGLUT2) in the arcuate, dorsomedial, and ventromedial nuclei of the hypothalamus of young (3 months), adult (12 months), and old male rats (24 months) was studied by Western blotting. In old rats, an increase in the expression of GAD65/67 in the arcuate and dorsomedial, VGLUT2 in the arcuate, dorsomedial, and ventromedial nuclei was observed. Thus, an increase in opposite processes of inhibition and excitation is observed in the hypothalamic nuclei during aging.

Spike Activity in the Ventromedial Nucleus of Rat Hypothalamus during Aging.

Spike activity of neurons in the ventromedial nucleus (VMN) of the hypothalamus in adult (6-8 months) and aged (2 years) male rats was studied by the in vivo extracellular method using stereotaxic insertion of microelectrodes. In all animals, firing frequency of most VMN neurons increased in response to glucose administration. However, in aged rats, the mean baseline and glucose-induced spike frequencies of VMN neurons were lower than in adult animals. These results support the hypothesis that aging is associated with a decrease in the functional activity of hypothalamic neurons.