Shamenko V. Functional State of the Vasopressinergic System of the Hypothalamus After Intermittent Hypoxic Hypoxia Influence.

he dissertation presents a theoretical justification and an experimental solution to an urgent scientific problem, which is to establish the mechanisms of the vasopressinergic system of the hypothalamus participation in the neuroendocrine response of the brain to the long term intermittent hypobaric hypoxic hypoxia and to study the features of the morphofunctional state of vasopressinergic neurons in the posthypoxic period. Based on quantitative immunohistochemical and immunofluorescence studies of serial sections of the hypothalamus, it was shown that the long term intermittent hypoxic hypoxia led to hypertrophy of the neurons of the lateral subdivision of the posterior magnocellular subnucleus of the paraventricular hypothalamic nucleus (PVNpml) with an increase in the area of the cytoplasm and nucleoli, as well as accumulation of cytoplasmic RNA. The increase of vasopressin concentration was noted in the magnocellular neurons and their axons, which led to a significant increase in the vasopressin total content in the PVNpml. Hypoxia resulted in an increase in immunoreactivity to cFos, HIF-1α, and HIF-3α proteins in the PVNpml in combination with an increase of these proteins’ concentration in neurocytes and an increase in the total content of these proteins within the subnuclei. An increase in the functional activity of neurons of the PVNpml with an increase of vasopressin synthesis and secretion in response to hypoxic stimulation was combined with an increase in the concentration of mRNA for the HIF-1α and HIF-3α proteins in the mediobasal hypothalamus. It is noteworthy that 10 days after the end of hypoxic conditions, signs of neurons hypertrophy were present in the PVNpml while RNA concentration increased in the nucleoli of neurocytes, and the main parameters of the neurosecretory activity of magnocellular neurons remained higher compared with the control parameters that indicated the prolongation of high functional activity of magnocellular vasopressinergic neurons in the posthypoxic period. Thus, the nature of PVNpml neurons functional activity alteration in response to hypoxia and in the posthypoxic period indicates the involvement of magnocellular vasopressinergic neurons in the processes of neuroendocrine adaptation to hypoxia.