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

Highlights • Exercise produces hypoxia in SNpc dopaminergic (DA) neurons. • Hif1α and Hif2α are modulated by exercise in the SNpc. • Loss of Hif1α in postnatal neurons results in lower DA numbers following exercise. • Hif2α loss in postnatal neurons lowers SNpc DA neuron number in standard condition...

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Veröffentlicht in:	Neuroscience 2015-06, Vol.295, p.23-38
Hauptverfasser:	Smeyne, M, Sladen, P, Jiao, Y, Dragatsis, I, Smeyne, R.J
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - metabolism beta-Galactosidase - metabolism Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism Cell Survival - genetics Dopaminergic Neurons - physiology exercise Gene Expression Regulation - drug effects Gene Expression Regulation - genetics Glial Fibrillary Acidic Protein - metabolism hypoxia Hypoxia-Inducible Factor 1, alpha Subunit - genetics Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Mice Mice, Inbred C57BL Mice, Knockout MPTP Poisoning - chemically induced MPTP Poisoning - genetics MPTP Poisoning - rehabilitation Neurology neuroprotection oxidative stress Pars Compacta - cytology Physical Conditioning, Animal - methods Platelet Endothelial Cell Adhesion Molecule-1 - metabolism preconditioning RNA, Messenger - metabolism RNA, Untranslated - genetics RNA, Untranslated - metabolism substantia nigra Tyrosine 3-Monooxygenase - metabolism
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Zusammenfassung:	Highlights • Exercise produces hypoxia in SNpc dopaminergic (DA) neurons. • Hif1α and Hif2α are modulated by exercise in the SNpc. • Loss of Hif1α in postnatal neurons results in lower DA numbers following exercise. • Hif2α loss in postnatal neurons lowers SNpc DA neuron number in standard conditions. • Exercise rescues the DA neuron loss mediated by Hif2α reduction.
ISSN:	0306-4522 1873-7544
DOI:	10.1016/j.neuroscience.2015.03.015