Purkinje cell degeneration elevates eupneic and hypercapnic ventilation in rats.
Previous studies have demonstrated that among cerebellar nuclei, the fastigial nucleus (FN) plays a major role in facilitation of respiration, especially during hypercapnia. Since the FN primarily receives inhibitory afferents from Purkinje cells (PCs), we hypothesized that degeneration of PCs would increase both eupneic and hypercapnic ventilation. Experiments were carried out on 20 animals (n=10 for both normal and PC-degenerated) that were divided into three groups based on the different preparations used, i.e., four pairs for the awake, three pairs for the anesthetized, and three other pairs initially for the awake and subsequently for the anesthetized. The awake normal and PCD rats were separately placed in an unrestrained whole-body plethysmograph and ventilatory parameters measured before (room air) and during hypercapnia (5% CO2 + 21% O2 + 74% N2) for 30 min. The anesthetized animals were exposed to the same level of hypercapnia applied for approximately 5 min. The results showed that both eupneic breathing and hypercapnia-induced ventilatory augmentation were significantly greater in the awake PCD rat than those observed in the normal one, primarily due to a remarkable elevation in VT with little changes in f. The same results were also observed in anesthetized preparations. A Fos protein Immunocytochemical approach was employed to determine the effect of degeneration on PCs and FN neuronal activity. Fos expression of PCs was very intensive in normal rats, but absent or diminished in PCD rats. In sharp contrast, FN Fos expression was obscure in normal rats, but very apparent in PCD rats. These data suggest that PCs play an inhibitory role in modulation of eupneic and hypercapnic ventilation via inhibiting FN neuronal activity.
Xu
Fadi
F
Department of Pathophysiology, Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108, USA. fxu@lrri.org
Zhou
Tongrong
T
Frazier
Donald T
DT
D000818:Animals; D016762:Genes, fos / Q000502:physiology; D006935:Hypercapnia / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology*; D012123:Pulmonary Ventilation / Q000502:physiology*; D011689:Purkinje Cells / Q000473:pathology* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley