Mild CIH Does Not Induce Cell Loss in the Substantia Nigra




Snyder, Brina
Davis, William
Cunningham, Rebecca


Journal Title

Journal ISSN

Volume Title



Purpose: Sleep apnea severity has been associated with Parkinson’s disease (PD) severity in men. Chronic intermittent hypoxia (CIH) is an animal model for sleep apnea. Mild CIH increases oxidative stress (OS) and inflammation in substantia nigral dopamine neurons, a neuron type lost in PD. Currently there is no model for early stage PD, wherein cell loss is not evident. Clinical symptoms of PD are not observed until about 80% of the substantia nigra (SN) is lost. It is unknown what causes PD, nor is there a cure for PD. The purpose of this study was to determine if CIH impacted neuronal viability in the SN in order to establish an early stage PD model. Methods: Gonadally intact male Sprague Dawley rats were exposed to either room air (normoxia) or six-minute chronic intermittent hypoxia (CIH) cycles, during which oxygen levels were rapidly decreased from 21% to 10% then returned to normal room air levels, eight hours a day during the light phase for seven days. Animals were perfused and brain tissue containing the SN was prepared for 8-OhDg (OS damage marker) and DAPI (cell nuclear marker) immunohistochemical staining. Afterwards, tissue sections were mounted and imaged to analyze the specific effects of CIH on OS damage, cell nuclear size, and cell number. Specifically, 8-OhDg and DAPI expression within the SN were summed and averaged across multiple sections of the SN. Comparisons were made between normoxia and CIH groups. In addition to OS damage and cell number, cell nuclear sizes were quantified and averaged across sections. 8-OhDg and DAPI staining were visualized using a digital camera on fluorescent microscope. Results: CIH increased OS, as shown by increased 8-OhDg expression, in the SN compared to normoxia. No significant differences in cell number or cell nuclear size were found between CIH and normoxia. Conclusions: This is the first study to show that mild CIH does not alter SN cell number or nuclear size, even though CIH increases OS damage in cells. These results support the use of CIH as an early stage animal model for PD. Data generated from this model aid in the understanding of the PD and its pathophysiology.