Correlation between neuroanatomical and respiratory functional changes in a Parkinson's disease model.

Abstract

Parkinson's disease (PD) is a disorder characterized by motor and non‐motor symptoms associated with loss of dopaminergic neurons in the compact part of the substantia nigra (SNc). However, other brainstem structures may also be degenerated, contributing to the appearance of non‐motor abnormalities, as breathing disorders that have a negative impact on the life's quality of those individuals. The aim of this study was to perform a temporal correlation between respiratory and neuroanatomical changes in an experimental model of PD. Adult male Wistar rats, with bilateral injections of 6‐hydroxy‐dopamine (6‐OHDA, 24 μg/μl) or vehicle into the striatum were used. At 30, 40 and 60 days after PD induction, the animals had functional and neuroanatomical parameters assessed by whole body plethysmography and immunohistochemical analysis. The results showed that in this model there are more than 70% of reduction in the dopaminergic neurons of the SNc and a reduction in the resting respiratory frequency (40 days: 88 ± 2 and 60 days: 81 ± 2, vs. vehicle 113 ± 2, bpm) and ventilation (40 days: 643 ± 29 and 60 days: 377 ± 21, vs. vehicle 877 ± 48 ml/kg/min) from 40 days after PD‐induction. A reduction in the hypercapnia‐induced respiratory frequency (fR: 40 days: 115 ± 4 and 60 days: 120 ± 3, vs. vehicle 131 ± 2 bpm) and ventilation (VE: 40 days: 1138 ± 96 and 60 days: 701 ± 66, vs. vehicle 1414 ± 102 ml/kg/min) was also observed in the same period. The neuroanatomical results showed that there was a reduction in the number of Phox2b neurons from 30 days after the injury in the nucleus of the solitary tract (NTS: 46%) and retrotrapezoid nucleus (RTN: 55%) and a reduction in the density of glial fibrillary acidic protein (GFAP) in the region of the rostral ventral respiratory group (rVRG: 39.3%). At 40 days, a reduction in the density of receptors for neurokinin‐1 (NK1R) was also observed in the pre‐Botzinger Complex (preBotC: 25%) and in the rVRG (38%) and in the density of GFAP in the RTN region (40.7%). At 60 days, the reduction in the densitity of GFAP was also present in the regions of preBotC (51.9%) and NTS (47.4%). The present results show that the neuroanatomical changes start before functional respiratory deficits and can be a cause for respiratory problems observed in PD.Support or Funding InformationFAPESP, CNPq and CAPES.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.