Raphe Pallidus is Not Important to Central Chemoreception in a Rat Model of Parkinson’s Disease

Abstract

Central chemoreceptors are primarily sensitive to changes in CO2/H+, and such changes lead to intense breathing activity. Medullary raphe and retrotrapezoid nucleus (RTN) neurons are candidates for central chemoreceptors because they are unusually pH sensitive. The pathophysiology of Parkinson’s disease (PD) is related to the reduction of neurons in the substantia nigra pars compacta (SNpc) that express dopamine, although other neurons can also be degenerated in this pathology. In rodent models of PD, we showed an impairment of the hypercapnia ventilatory response due to a reduction in the number of RTN chemosensitive neurons. Here, we aimed to investigate if serotonine-expressing neurons in the Raphe pallidus/parapyramidal region (RPa/PPy) are also involved in the modulation of breathing during central chemoreception activation in a PD animal model. PD was induced in male Wistar rats with bilateral injection of 6-OHDA (6-hydroxydopamine; 24 µg/µl) into the striatum, which leads to a reduction in the catecholaminergic neurons of the SNpc by 89%. In PD animals, we noticed a reduction in the number of RPa neurons that project to the RTN, without a change in the number of hypercapnia-activated (7% CO2) raphe neurons. The PD animals that received injection of the toxin saporin anti-SERT into the RPA/PPy region did not show a further reduction of respiratory frequency (fR) or ventilation (VE) at rest or during hypercapnia challenge. These experiments demonstrate that serotonergic neurons of RPa/PPy are not involved in the breathing responses induced by central chemoreceptor activation in a PD animal model.