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Purkinje cell degeneration elevates eupneic and hypercapnic ventilation in rats

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Abstract

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 ∼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.

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Authors and Affiliations

  1. Department of Pathophysiology, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive, SE, 87108, Albuquerque, New Mexico, USA

    Fadi Xu & Tongrong Zhou

  2. Department of Physiology, School of Medicine, University of Kentucky, Lexington, Kentucky, USA

    Donald T. Frazier

Authors
  1. Fadi Xu
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  2. Tongrong Zhou
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  3. Donald T. Frazier
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Correspondence to Fadi Xu.

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Xu, F., Zhou, T. & Frazier, D.T. Purkinje cell degeneration elevates eupneic and hypercapnic ventilation in rats. Cerebellum 3, 133–140 (2004). https://doi.org/10.1080/14734220310023332

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  • DOI: https://doi.org/10.1080/14734220310023332

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