Abstract
Neurogenesis, especially neurite outgrowth is an essential element of neuroplasticity after cerebral ischemic injury. Mitochondria may supply ATP to power fundamental developmental processes including neuroplasticity. Although rosuvastatin (RSV) displays a potential protective effect against cerebral ischemia, it remains unknown whether it modulates mitochondrial biogenesis and function during neurite outgrowth. Here, the oxygen-glucose deprivation (OGD) model was used to induce ischemic injury. We demonstrate that RSV treatment significantly increases neurite outgrowth in cortical neurons after OGD-induced damage. Moreover, we show that RSV reduces the generation of reactive oxygen species (ROS), protects mitochondrial function, and elevates the ATP levels in cortical neurons injured by OGD. In addition, we found that, under these conditions, RSV treatment increases the mitochondrial DNA (mtDNA) content and the mRNA levels of mitochondrial transcription factor A (TFAM) and nuclear respiratory factor 1 (NRF-1). Furthermore, blocking Notch1, which is expressed in primary cortical neurons, reverses the RSV-dependent induction of mitochondrial biogenesis and function under OGD conditions. Collectively, these results suggest that RSV could restore neurite outgrowth in cortical neurons damaged by OGD in vitro, by preserving mitochondrial function and improving mitochondrial biogenesis, possibly through the Notch1 pathway.
Highlights
Stroke is one of the leading causes of long-term disability and death worldwide and affects the patients’ emotional, mental and physical health (Thampy and Pais, 2016)
Based on our finding that RSV preserved the mitochondrial function in primary cultured neurons exposed to oxygen-glucose deprivation (OGD), we explored whether Notch1 was involved in this process
Previous studies have indicated that RSV might impair mitochondrial function and biogenesis (Broniarek and Jarmuszkiewicz, 2016), our results show that RSV treatment restores the OGD-induced Mitochondrial DNA (mtDNA) loss in cortical neurons
Summary
Stroke is one of the leading causes of long-term disability and death worldwide and affects the patients’ emotional, mental and physical health (Thampy and Pais, 2016). Targeting neurite outgrowth represents a prospective therapeutic strategy for stroke patients. Rosuvastatin Improves Neurite Outgrowth and glucose supply, which is caused by stroke and mimicked by the in vitro oxygen-glucose deprivation (OGD) model, can produce a large number of reactive oxygen species (ROS) and lead to the depletion of cellular ATP (Rousset et al, 2015). Numerous studies have shown that mitochondrial dysfunction, especially regarding biogenesis, plays a crucial role in ischemic injury (McLeod et al, 2005; Gutsaeva et al, 2008). Identifying pharmacological agents that preserve mitochondrial functions and promote neurite outgrowth against cerebral ischemic injury might be an ideal therapeutic strategy
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