Exercise training abrogates age-dependent loss of hypothalamic oxytocinergic circuitry and maintains high parasympathetic activity.

Abstract

Neuroanatomical studies associating neuronal tract tracing and immunohistochemistry identified reciprocal (ascending noradrenergic/descending oxytocinergic, OTergic) connections between brainstem cardiovascular nuclei and the paraventricular hypothalamic nucleus (PVN). Previous functional studies indicated that exercise training (T) augmented the expression/activity of OTergic pathway and improve the autonomic control of the heart. Knowing that ageing is associated with autonomic dysfunction and sinoaortic denervation blocked T-induced beneficial effects, we hypothesized that T was able to reduce age-dependent impairment by improving the afferent signaling to PVN and augmenting OTergic modulation of cardiovascular control. We evaluated the combined effects of T and age on plastic remodeling of ascending dopamine β-hydroxylase (DBH+) and descending OT+ pathways and correlated them with cardiovascular parameters. Male Wistar rats were submitted to T or kept sedentary for 8 weeks. After evaluating arterial pressure, heart rate (HR), their variabilities and spectral components in conscious rats at rest, brains were harvested to analyze the plastic remodeling of brain autonomic nuclei (immunofluorescence + confocal microscopy). The density of DBH+ neurons within the nucleus of solitary tract (NTS) and caudal ventrolateral medulla, the number of DBH+ terminals overlapping OT+ neurons in PVN preautonomic nuclei, as well as the density of OT+ neurons and their projections to NTS and dorsal motor nucleus of the vagus were markedly reduced in S rats during 8-weeks of inactivity In contrast, these effects were completely blocked by T and reversed to a large augmentation of DBH+ and OT+ densities in both cell bodies and terminals within autonomic nuclei and target areas. All plastic changes observed correlated positively with parasympathetic activity to the heart (HF-PI, but not with LF-PI) and negatively with resting HR. Data indicate that T, by increasing beneficial neuroplastic adaptive changes within brainstem-PVN reciprocal network, abrogates age-dependent deleterious remodeling and augments parasympathetic modulation of the heart, therefore improving autonomic function. This article is protected by copyright. All rights reserved.