Research PaperRole of the locus coeruleus catecholaminergic neurons in the chemosensory control of breathing in a Parkinson's disease model

- Parkinson´s disease (PD) is associated with respiratory dysfunction.
- a rat model of PD has a reduced chemosensory control of breathing compared with age-matched control rats.
- PD animals have more fos-activated neurons in the LC and a reduced number in the RTN neurons during high levels of CO2.
- selective depletion of LC neurons in PD animals further reduced the chemosensory control of breathing in conscious animals.

A previous study has demonstrated that in the 6-hydroxydopamine (6-OHDA)-model of Parkinson's disease (PD) there is a reduction in the number of Phox2b neurons in the retrotrapezoid nucleus (RTN) and a decrease in the respiratory response to hypercapnia 40 days after PD-induction. The functional deficiency is restored 60 days after 6-OHDA injection and here we tested the hypothesis that the locus coeruleus (LC) could be a candidate to restore the breathing deficiency. Minute Ventilation (VE) in response to hypercapnia (7% CO2) was assessed one day before, and then 40 and 60 days after bilateral 6-OHDA (24 μg/μL) or vehicle injections into the LC in control or PD-induced male Wistar rats. Bilateral injections of 6-OHDA decreased catecholaminergic neurons by 86% and 83% in the substantia nigra pars compacta (SNpc) and LC, respectively. As already described, in animals with lesions to the SNpc (N = 6/group), the reduction in the ventilatory response to hypercapnia was restored 60 days after PD (1257 ± 81 vs. vehicle: 1185 ± 49 mL/kg/min). However, in animals with PD and lesion in the LC, the ventilation was blunted (674 ± 39 mL/kg/min). In another group of PD rats, we observed a reduction in the number of hypercapnia-induced-fos+ cells in the RTN region (40 days: 38 ± 3 and 60 days: 8.5 ± 0.9 vs. vehicle 78 ± 3 cells) and an increase in the LC (40 days: 46 ± 4 and 60 days: 94 ± 22 vs. vehicle 1 ± 1 cells). Our data suggest that LC catecholaminergic neurons can be a candidate structure mediating chemoreceptor function in a model of PD.