Respiratory deficits in a female rat model of Parkinson's disease

Abstract

Emerging evidence indicates that the course of Parkinson’s disease (PD) includes auto-nomic and respiratory deficiencies in addition to the classical motor symptoms. Theprevalence of PD is lower in women, and it has been hypothesized that neuroprotectionby ovarian hormones can explain this difference. While male PD animal models pre-sent changes in the central respiratory control areas, as well as ventilatory parametersunder normoxia and hypercapnia, little is known about sex differences regardingrespiratory deficits in this disease background. This study aimed to explore the neuro-anatomical and functional respiratory changes in intact and ovariectomized (OVX)female rats subjected to chemically induced PD via a bilateral intrastriatal injectionof 6-hydroxydopamine (6-OHDA). The respiratory parameters were evaluated bywhole-body plethysmography, and the neuroanatomy was monitored using immuno-histochemistry. It was found that dopaminergic neurons in the substantia nigraand neurokinin-1 receptor density in the rostral ventrolateral respiratory group,Bötzinger and pre-Bötzinger complex were reduced in the chemically induced PDanimals. Additionally, reduced numbers of Phox2b neurons were only observed in theretrotrapezoid nucleus of PD-OVX rats. Concerning respiratory parameters, in OVXrats, the resting and hypercapnia-induced tidal volume (VT ) is reduced, and ventilation(̇ VE ) changes independently of 6-OHDA administration. Notably, there is a reductionin the number of retrotrapezoid nucleus Phox2b neurons and hypercapnia-inducedrespiratory changes in PD-OVX animals due to a 6-OHDA and OVX interaction. Theseresults suggest a protective effect induced by ovarian hormones in neuroanatomicalchanges observed in a female experimental PD model.