title: Respiratory deficits in a rat model of Parkinson's disease.
abstract: Parkinson's disease (PD) is a neurodegenerative disease characterized by loss of the dopaminergic nigrostriatal pathway. In addition to deficits in voluntary movement, PD involves a disturbance of breathing regulation. However, the cause and nature of this disturbance are not well understood. Here, we investigated breathing at rest and in response to hypercapnia (7% CO2) or hypoxia (8% O2), as well as neuroanatomical changes in brainstem regions essential for breathing, in a 6-hydroxydopamine (6-OHDA) rat model of PD. Bilateral injections of 6-OHDA (24μg/μl) into the striatum decreased tyrosine hydroxylase (TH(+))-neurons in the substantia nigra pars compacta (SNpc), transcription factor phox2b-expressing neurons in the retrotrapezoid nucleus and neurokinin-1 receptors in the ventral respiratory column. In 6-OHDA-lesioned rats, respiratory rate was reduced at rest, leading to a reduction in minute ventilation. These animals also showed a reduction in the tachypneic response to hypercapnia, but not to hypoxia challenge. These results suggest that the degeneration of TH(+) neurons in the SNpc leads to impairment of breathing at rest and in hypercapnic conditions. Our data indicate that respiratory deficits in a 6-OHDA rat model of PD are related to downregulation of neural systems involved in respiratory rhythm generation. The present study suggests a new avenue to better understand the respiratory deficits observed in chronic stages of PD.
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Tuppy
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
authors.forename: B F
authors.initials: BF
authors.lastname: Barna
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Alves-Dos-Santos
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
authors.forename: L R G
authors.initials: LR
authors.lastname: Britto
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
authors.forename: S
authors.initials: S
authors.lastname: Chiavegatto
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
authors.forename: T S
authors.initials: TS
authors.lastname: Moreira
authors.affiliation: Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, SP, Brazil. Electronic address: takakura@icb.usp.br.
authors.forename: A C
authors.initials: AC
authors.lastname: Takakura
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D002452:Cell Count; D003342:Corpus Striatum / Q000187:drug effects*; D004195:Disease Models, Animal; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D019344:Lactic Acid / Q000097:blood; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000150:complications* / Q000209:etiology; D011597:Psychomotor Performance; D012123:Pulmonary Ventilation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D012120:Respiration Disorders / Q000209:etiology*; D012125:Respiratory Center / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
chemical_list: D018663:Adrenergic Agents; D018040:Receptors, Neurokinin-1; D019344:Lactic Acid; D016627:Oxidopamine
keywords: Parkinson’s disease; brainstem; breathing; hypercapnia; hypoxia