Correlation between neuroanatomical and functional respiratory changes observed in an experimental model of Parkinson's disease

Abstract

New findings: What is the central question of this study? What is the relationship between neuroanatomical and functional respiratory changes in an experimental model of Parkinson's disease? What is the main finding and its importance? Sixty days after induction of Parkinson's disease in a rat model, there are decreases in baseline breathing and in the number of neurons, density of the neurokinin-1 receptor and density of astrocytes in the ventrolateral respiratory region. These results provide the first evidence that neuroanatomical changes occur before functional respiratory deficits in a Parkinson's disease model and that there is a positive correlation between those sets of changes. The neuroanatomical changes impair respiratory activity and are presumably a major cause of the respiratory problems observed in Parkinson's disease.

Abstract: We showed previously that 60 days after the induction of Parkinson's disease (PD) in a rat model, there are decreases in baseline breathing and in the number of phox2b-expressing neurons of the retrotrapezoid nucleus (RTN) and nucleus of the solitary tract (NTS), as well as a reduction in the density of the neurokinin-1 receptor (NK1r) in the pre-Bötzinger complex (preBötC) and rostral ventrolateral respiratory group (rVRG). Here, our aim was to evaluate the correlation between neuroanatomical and functional respiratory changes in an experimental model of PD. Male Wistar rats with bilateral injections of 6-hydroxydopamine (6-OHDA, 24 μg μl^-1 ) or vehicle into the striatum had respiratory parameters assessed by whole-body plethysmography 1 day before and 30, 40 or 60 days after the ablation. From the 30th day after the ablation, we observed a reduction in the number of phox2b neurons in the RTN and NTS and a reduction in the density of astrocytes in the rVRG. At 40 days after the ablation, we observed decreases in the density of NK1r in the preBötC and rVRG and of astrocytes in the RTN region. At 60 days, we observed a reduction in the density of astrocytes in the NTS and preBötC regions. The functional data showed changes in the resting and hypercapnia-induced respiratory rates and tidal volume from days 40-60 after injury. Our data suggest that the neuroanatomical changes impair respiratory activity and are presumably a major cause of the respiratory problems observed in PD.

Keywords: 6-OHDA; astrocyte; breathing; central chemoreception; retrotrapezoid nucleus.