Rosuvastatin Improves Neurite Outgrowth of Cortical Neurons against Oxygen-Glucose Deprivation via Notch1-mediated Mitochondrial Biogenesis and Functional Improvement

• Main Authors: Weiliang He, Yingping Liu, Xiaochao Tian
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2018-01-01
• Series: Frontiers in Cellular Neuroscience
• Subjects: cortical neurons; neurite outgrowth; cerebral ischemia; rosuvastatin; mitochondria; notch1
• Online Access: http://journal.frontiersin.org/article/10.3389/fncel.2018.00006/full

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.