| First Author | Smeyne M | Year | 2015 |
| Journal | Neuroscience | Volume | 295 |
| Pages | 23-38 | PubMed ID | 25796140 |
| Mgi Jnum | J:222648 | Mgi Id | MGI:5645174 |
| Doi | 10.1016/j.neuroscience.2015.03.015 | Citation | Smeyne M, et al. (2015) HIF1alpha is necessary for exercise-induced neuroprotection while HIF2alpha is needed for dopaminergic neuron survival in the substantia nigra pars compacta. Neuroscience 295:23-38 |
| abstractText | Exercise reduces the risk of developing a number of neurological disorders and increases the efficiency of cellular energy production. However, overly strenuous exercise produces oxidative stress. Proper oxygenation is crucial for the health of all tissues, and tight regulation of cellular oxygen is critical to balance O2 levels and redox homeostasis in the brain. Hypoxia Inducible Factor (HIF)1alpha and HIF2alpha are transcription factors regulated by cellular oxygen concentration that initiate gene regulation of vascular development, redox homeostasis, and cell cycle control. HIF1alpha and HIF2alpha contribute to important adaptive mechanisms that occur when oxygen and ROS homeostasis become unbalanced. It has been shown that preconditioning by exposure to a stressor prior to a hypoxic event reduces damage that would otherwise occur. Previously we reported that 3 months of exercise protects SNpc dopaminergic (DA) neurons from toxicity caused by Complex I inhibition. Here, we identify the cells in the SNpc that express HIF1alpha and HIF2alpha and show that running exercise produces hypoxia in SNpc DA neurons, and alters the expression of HIF1alpha and HIF2alpha. In mice carrying a conditional knockout of Hif1alpha in postnatal neurons we observe that exercise alone produces SNpc TH+ DA neuron loss. Loss of HIF1alpha also abolishes exercise-induced neuroprotection. In mice lacking Hif2alpha in postnatal neurons, the number of TH+ DA neurons in the adult SNpc is diminished, but 3months of exercise rescues this loss. We conclude that HIF1alpha is necessary for exercise-induced neuroprotection and both HIF1alpha and HIF2alpha are necessary for the survival and function of adult SNpc DA neurons. |
