Poly (ADP-ribose) polymerase plays an important role in intermittent hypoxia-induced cell death in rat cerebellar granule cells

Cerebellar granule cells were freshly prepared from neonatal Sprague-Dawley rats. IH was created by culturing the cerebellar granule cells in the incubators with oscillating O2 concentration at 20% and 5% every 30 min for 1-4 days. The results of this study are based on image analysis using a confocal microscope and associated software. Cellular oxidative stress increased with increase in IH. In addition, the occurrence of cell death (apoptosis and necrosis) increased as the duration of IH increased, but decreased in the presence of an iron chelator (phenanthroline) or poly (ADP-ribose) polymerase (PARP) inhibitors [3-aminobenzamide (3-AB) and DPQ]. The fluorescence of caspase-3 remained the same regardless of the duration of IH, and Western blots did not detect activation of caspase-3. However, IH increased the ratio of apoptosis-inducing factor (AIF) translocation to the nucleus, while PARP inhibitors (3-AB) reduced this ratio.According to our findings, IH increased oxidative stress and subsequently leading to cell death. This effect was at least partially mediated by PARP activation, resulting in ATP depletion, calpain activation leading to AIF translocation to the nucleus.We suggest that IH induces cell death in rat primary cerebellar granule cells by stimulating oxidative stress PARP-mediated calpain and AIF activation.Sleep apnea is a major public health problem in Western and Asian countries [1]. Obstructive sleep apnea [2] is the most prevalent type of sleep apnea. Patients with OSA are at increased risk of cardiovascular diseases and neuro-cognitive deficits [3,4]. Magnetic resonance imaging studies in OSA patients have revealed significant reductions in gray matter of several brain regions, including the cortex, hippocampus, and cerebellum [5].Episodic cessation of airflow during sleep in patients with OSA results in intermittent hypoxia (IH) [1], which cycles through periods of hypoxia and reoxygenation. Reoxygenation increases the risk of oxidative stres