Pharmacological Correction of Alterations in Apoptosis of Neurons of the Hypothalamic Suprachiasmatic Nucleus and Pinealocytes in Rats during Aging and under Stress

Abstract

The pineal gland is known to play an important role in adaptogenesis. The hypothalamus is one of the main links of the stress-reactive system; it participates in the regulation of the involution of the whole body. Thus, the study of changes in these organs under stress and during aging is of considerable interest. The goal of this work is to study the apoptosis mechanisms of pinealocytes and neurosecretory cells of the hypothalamic suprachiasmatic nucleus in aging, under stress, and during pharmacological correction of involutional processes and stress response (antioxidant α-tocopherol acetate, immunomodulator Cycloferon). Young (10–12 months) and old (24–30 months) Wistar rats were used as the model organism. Age-related features of the dynamics of apoptosis of pinealocytes and neurosecretory cells of the hypothalamic suprachiasmatic nucleus were studied via TUNEL and immunohistochemistry, and the potential for the pharmacological correction of apoptotic processes were determined. An age-dependent increase in the level of apoptosis of cells of the suprachiasmatic nucleus and pineal gland in rats was revealed. Stress (immobilization) led to increased cell death, which was more significant in older animals. This indicates that the pineal gland and suprachiasmatic nucleus, traditionally regarded as regulators of circadian rhythms, are also actively involved in general adaptation processes. The studied drugs (α-tocopherol-acetate, Cycloferon, and their combination) have a pronounced antiapoptotic, cytoprotective effect under physiological conditions during aging and under nonspecific emotional stress (immobilization) in young and old animals. The regulatory effect is implemented via activation of the expression of the antiapoptotic protein Bcl-2 in neurosecretory cells of the suprachiasmatic nucleus and pinealocytes.