Date of Award
Doctor of Philosophy
Helen J Sable
J Gayle Beck
Sudden unexplained death occurs in multiple populations. Significant evidence suggests fatality was due to cardiorespiratory failure--likely in response to an exogenous stressor which created an immediate hypercapnic (increased carbon dioxide) or hypoxic (decreased oxygen) environment. Research into the mechanism(s) of failure has focused on the brainstem (the classic cardiorespiratory control center) to no avail. Recently, research has probed outside of the brainstem to identify structures that may play a specific modulatory role during stressful conditions such as hypoixia and hypercapnia, for example the cerebellum, which houses a pair of chemosensitive nuclei, the fastigial nuclei (FN). As the Purkinje cells of the cerebellar vermis primarily innervate the FN, and global cerebellar Purkinje cell loss inhibits the abiliity to respond to and recover frommild hypoxic and hypercapnic stressors, the purpose of this study was to examine the respiratory responses of multiple animal models of developmental cerebellar Purkinje cell loss or dysfunction to hypoxic and hypercapnic stressors. It was hypothesized that cerebellar Purkinje cell loss or dysfunction, regardless of extent, would result in a reduced ability to resond to and recover from hypoxic and hypercapnic stressors. Twelve male sibling mutant and wildtype mouse pairs from three strains (Fmr1, Lurcher, and mdx) on three different genetic backgrounds (FVB, B6, and B10 respectively) were exposed to multiple environmental stressors with periods of recovery in normal room air in a whole body plethysmography system. Respiratory minute ventilation (MV) patterns were examined for changes in depth of breathing, breath frequency, and pausing between breaths. Results of multiple mixed analyses of covariance indicated all animals responded accordingly to the hypoxic and hypercapnic stressors by increasing their MV and subsequently decreasing MV when allowed to recover in normal conditions. However, regardless of strain, all mutant animals with cerebellar Purkinje cell loss or dysfunction were slower to respond to stressors and revealed patterns of disordered breathing during recovery. As cerebellar Purkinje cell loss or dysfunction and disordered breathing are common in multiple populations at risk for sudden unexplained death, the precise role of this neuropathology in the fatal event of sudden death victims should be further investigated.
dissertation or thesis originally submitted to the local University of Memphis Electronic Theses & dissertation (ETD) Repository.
Calton, Michele Ann, "Compensatory Respiratory Effects in Three Mouse Models of Developmental Cerebellar Neuropathology during Exposure to and Recovery from Hypoxic and Hypercapnic Challenges" (2016). Electronic Theses and Dissertations. 1461.