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Carotid body dysfunction and altered oxygen homeostasis in models of Parkinson's disease
Author(s) -
Gillum Matthew Paul,
Azam Iram T.,
Wehner Mackenzie R.,
Hodges Matthew R.,
MaguireZeiss Kathleen A.,
Federoff Howard J.,
Richerson George B.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1231.5
Subject(s) - carotid body , hypoxia (environmental) , homeostasis , hypoxic ventilatory response , dopaminergic , medicine , parkinson's disease , parkinsonism , cardiology , endocrinology , dopamine , disease , respiratory system , oxygen , chemistry , carotid arteries , organic chemistry
For reasons that are not well understood, patients with Parkinson's disease (PD) are three times more likely to die from respiratory illnesses. Because a hallmark of PD is the degeneration of select dopaminergic neurons, and because PD patients do not increase ventilation normally in response to hypoxia, we investigated the hypothesis that the carotid body—a key regulator of O 2 homeostasis situated at the bifurcation of the carotid artery in the neck and rich in dopamine—is susceptible to dysfunction in experimental models of Parkinsonism. Normally, mice respond to hypoxia by increasing ventilation and/or decreasing oxygen consumption (VO 2 ). However, we found that treatment with the dopaminergic neurotoxin MPP+ completely attenuated the normal ventilatory increase in response to hypoxia. In contrast, we report that α‐synuclein double mutant mice—a transgenic PD model—fail to decrease VO 2 during hypoxia and as a result must ventilate more to compensate. If carotid body dysfunction also occurs in patients with PD, then impaired sensitivity to hypoxia and further failure to reduce metabolic oxygen demand in conditions of low O 2 might promote mortality, especially in cases of lung disease like pneumonia when signals from the carotid body and a global decrease in oxygen consumption become critical.