HIF1α is necessary for exercise-induced neuroprotection while HIF2α is needed for dopaminergic neuron survival in the substantia nigra pars compacta

Neuroscience
M SmeyneRichard J Smeyne

Abstract

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)1α and HIF2α are transcription factors regulated by cellular oxygen concentration that initiate gene regulation of vascular development, redox homeostasis, and cell cycle control. HIF1α and HIF2α 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 HIF1α and HIF2α and show that running exercise produces hypoxia in SNpc DA neurons, and alters the expression of HIF1α and HIF2α. In mice carrying a conditional knockout of Hif1α in postnatal neurons we observe that exercise al...Continue Reading

References

Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·G L WangG L Semenza
Jun 2, 1995·The Journal of Biological Chemistry·A P LevyM A Goldberg
Jan 20, 1995·The Journal of Biological Chemistry·G L Wang, G L Semenza
May 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·G L Wang, G L Semenza
Dec 1, 1996·Neurodegeneration : a Journal for Neurodegenerative Disorders, Neuroprotection, and Neuroregeneration·D C GermanP K Sonsalla
Sep 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·N S ChandelP T Schumacker
Mar 21, 2000·Genesis : the Journal of Genetics and Development·I Dragatsis, S Zeitlin
Jul 6, 2000·Proceedings of the National Academy of Sciences of the United States of America·J PengG H Fong
Aug 30, 2000·The Journal of Biological Chemistry·F H AganiJ C LaManna
Mar 30, 2001·The Journal of Biological Chemistry·Z DongJ Nishiyama
Oct 13, 2001·Science·R K Bruick, S L McKnight
May 17, 2002·Journal of Applied Physiology·Imanuel LermanLeslie A Leinwand
Jun 11, 2002·American Journal of Physiology. Cell Physiology·Faton H AganiJoseph LaManna
Jun 28, 2002·Trends in Neurosciences·Carl W Cotman, Nicole C Berchtold
Aug 10, 2004·The Journal of Experimental Biology·Joseph C LaMannaPaola Pichiule
Sep 24, 2004·Physiological Genomics·J Timothy LightfootSteven R Kleeberger
Mar 26, 2005·Brain Research. Molecular Brain Research·Richard Jay Smeyne, Vernice Jackson-Lewis
May 28, 2005·Glia·Michelle SmeyneRichard J Smeyne
Jul 19, 2005·Neuroscience Letters·Jie LiYuchuan Ding
Aug 2, 2005·Cell Metabolism·Joslyn K BrunelleNavdeep S Chandel
Sep 15, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Juan C ChavezPaola Pichiule
Dec 27, 2006·Free Radical Biology & Medicine·Navdeep S Chandel, G R Scott Budinger
Sep 18, 2007·Ageing Research Reviews·Zsolt RadakSataro Goto
Apr 21, 2009·European Journal of Pharmacology·Masamichi TajimaHiroshi Sakagami
Feb 2, 2010·Brain Research·Kimberly M GereckeRichard J Smeyne
Feb 10, 2010·Journal of Neuroscience Research·Elena GammellaLorenza Tacchini
May 7, 2011·Cell Death and Differentiation·C-Y KoC-H Hu

❮ Previous
Next ❯

Citations

Dec 23, 2017·GeroScience·Joanna M S DaviesKelvin J A Davies
Nov 6, 2017·Brain Structure & Function·Justin N WeilnauRehana K Leak
Nov 23, 2017·Frontiers in Aging Neuroscience·Lijuan HouFu-Ming Zhou
Jan 23, 2020·Scientific Reports·William R ReayMurray J Cairns
Jul 9, 2020·Frontiers in Aging Neuroscience·Grace F Crotty, Michael A Schwarzschild
Sep 13, 2020·Brain Structure & Function·Morgan E StevensonRodney A Swain
Dec 15, 2018·Journal of Neuroscience Research·Robert P Ostrowski, John H Zhang

❮ Previous
Next ❯

Related Concepts

Related Feeds

Astrocytes in Parkinson Disease

Parkinson's disease (PD) is a neurodegenerative disorder caused by the progressive loss of dopaminergic neurons. Some PD-genes may be associated with astrocyte dysfunction. Discover the latest research on astrocytes in Parkinson's disease here.

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Amygdala and Midbrain Dopamine

The midbrain dopamine system is widely studied for its involvement in emotional and motivational behavior. Some of these neurons receive information from the amygdala and project throughout the cortex. When the circuit and transmission of dopamine is disrupted symptoms may present. Here is the latest research on the amygdala and midbrain dopamine.

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.