Erythropoietin Upregulates Brain Hemoglobin Expression and Supports Neuronal Mitochondrial Activity

Molecular Neurobiology
Naveen Kumar SinghalJennifer McDonough

Abstract

Multiple sclerosis (MS) is a neuro-inflammatory and demyelinating disease. Downregulation of neuronal mitochondrial gene expression and activity have been reported in several studies of MS. We have previously shown that hemoglobin-β (Hbb) signals to the nucleus of neurons and upregulates H3K4me3, a histone mark involved in regulating cellular metabolism and differentiation. The present study was undertaken to evaluate the effect of erythropoietin (EPO) on the upregulation of hemoglobin and mitochondrial-associated neuroprotection. We found that administering EPO (5000 IU/kg intraperitoneally) to mice upregulated brain Hbb expression, levels of H3K4me3, expression of mitochondrial complex III, complex V, and mitochondrial respiration. We also found that the neuronal mitochondrial metabolite N-acetylaspartate (NAA), a marker of neuronal mitochondrial activity, was increased with EPO treatment. Further, we measured the effects of EPO on preventing mitochondrial deficits in the cuprizone toxic demyelinating mouse model of MS. We found that EPO prevented cuprizone-mediated decreases in Hbb, complex III, and NAA. Our data suggest that EPO mediated regulation of Hbb supports neuronal energetics and may provide neuroprotection in MS an...Continue Reading

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Citations

Mar 17, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Guokun ZhouXiang-Ming Zha
Jan 10, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Chitra SubramanianSuzanne Jackowski
Aug 7, 2021·Communications Biology·Robert A JacobsEdith M Schneider Gasser

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Methods Mentioned

BETA
Assay
electrophoresis
co-IP

Software Mentioned

Agilent Chemstation

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