Title

Impaired hypercarbic and hypoxic responses from developmental loss of cerebellar purkinje neurons: implications for sudden infant death syndrome.

Document Type

Article

Publication Date

12-2014

JAX Source

Cerebellum 2014 Dec; 13(6):739-50.

PMID

25132500

Abstract

Impaired responsivity to hypercapnia or hypoxia is commonly considered a mechanism of failure in sudden infant death syndrome (SIDS). The search for deficient brain structures mediating flawed chemosensitivity typically focuses on medullary regions; however, a network that includes Purkinje cells of the cerebellar cortex and its associated cerebellar nuclei also helps mediate responses to carbon dioxide (CO2) and oxygen (O2) challenges and assists integration of cardiovascular and respiratory interactions. Although cerebellar nuclei contributions to chemoreceptor challenges in adult models are well described, Purkinje cell roles in developing models are unclear. We used a model of developmental cerebellar Purkinje cell loss to determine if such loss influenced compensatory ventilatory responses to hypercapnic and hypoxic challenges. Twenty-four Lurcher mutant mice and wild-type controls were sequentially exposed to 2 % increases in CO2 (0-8 %) or 2 % reductions in O2 (21-13 %) over 4 min, with return to room air (21 % O2/79 % N2/0 % CO2) between each exposure. Whole body plethysmography was used to continuously monitor tidal volume (TV) and breath frequency (f). Increased f to hypercapnia was significantly lower in mutants, slower to initiate, and markedly lower in compensatory periods, except for very high (8 %) CO2 levels. The magnitude of TV changes to increasing CO2 appeared smaller in mutants but only approached significance. Smaller but significant differences emerged in response to hypoxia, with mutants showing smaller TV when initially exposed to reduced O2 and lower f following exposure to 17 % O2. Since cerebellar neuropathology appears in SIDS victims, developmental cerebellar neuropathology may contribute to SIDS vulnerability. Cerebellum 2014 Dec; 13(6):739-50.

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