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

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 the OTergic pathway and improved the autonomic control of the heart. Knowing that ageing is associated with autonomic dysfunction and also that sinoaortic denervation blocked T-induced beneficial effects, we hypothesised that T was able to reduce age-dependent impairment by improving the afferent signalling to PVN and augmenting OTergic modulation of cardiovascular control. We evaluated the combined effects of T and age on plastic remodelling of ascending dopamine beta-hydroxylase (DBH)+ and descending oxytocin (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 analyse the plastic remodelling of brain autonomic nuclei (immunofluorescence + confocal microscopy). The density of DBH+ neurones within the nucleus of solitary tract (NTS) and caudal ventrolateral medulla, the number of DBH+ terminals overlapping OT+ neurones in PVN preautonomic nuclei, as well as the density of OT+ neurones and their projections to the NTS and dorsal motor nucleus of the vagus, were markedly reduced in sedentary rats during 8 weeks of inactivity. By 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 (high frequency pulse interval, but not with low frequency pulse interval) and negatively with resting HR. Data indicate that T, by increasing beneficial neuroplastic adaptive changes within the brainstem-PVN reciprocal network, abrogates age-dependent deleterious remodelling and augments parasympathetic modulation of the heart, therefore improving autonomic function.