1. Using cultured neurons, we manipulated intracellular sodium concentrations as a marker of activity. Increased intracellular sodium caused by monensin stimulated the sodium pump to consume ATP. Immediately thereafter, transcription of mitochondrial-derived enzymes for oxidative phosphorylation was upregulated, which would lead to increased ATP synthesis. This study identified the rapid coupling mechanism between electrical activity, ATP consumption and oxidative-phosphorylation activation in mitochondria for new ATP synthesis. (Mehrabian et al 2005). 2. As a model for heart sympathetic denervation in Parkinson disease, rats were sympathetically denervated with 6-hydroxydopamine (6-OHDA). Extending our in vivo model for the brain, we measured incorporation of palmitic and arachidonic acids into phospholipids of denervated and normal hearts. Incorporation of palmitic acid (from the acyl-CoA precursor pool) was unchanged, whereas incorporation of arachidonic acid was reduced by 70%, accompanied by a reduction in phospholipase A2 activity. It now would be of interest to see if Parkinson disease patients have this denervation defect, using positron emission tomography. (Patrick et al 2005)

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000399-01
Application #
7132265
Study Section
(BPM)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2005
Total Cost
Indirect Cost
Name
Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Krasemann, Susanne; Madore, Charlotte; Cialic, Ron et al. (2017) The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases. Immunity 47:566-581.e9
Rapoport, Stanley I (2013) Translational studies on regulation of brain docosahexaenoic acid (DHA) metabolism in vivo. Prostaglandins Leukot Essent Fatty Acids 88:79-85
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Rapoport, Stanley I; Rao, Jagadeesh S; Igarashi, Miki (2007) Brain metabolism of nutritionally essential polyunsaturated fatty acids depends on both the diet and the liver. Prostaglandins Leukot Essent Fatty Acids 77:251-61
Igarashi, Miki; Ma, Kaizong; Chang, Lisa et al. (2007) Dietary n-3 PUFA deprivation for 15 weeks upregulates elongase and desaturase expression in rat liver but not brain. J Lipid Res 48:2463-70
Igarashi, Miki; DeMar Jr, James C; Ma, Kaizong et al. (2007) Upregulated liver conversion of alpha-linolenic acid to docosahexaenoic acid in rats on a 15 week n-3 PUFA-deficient diet. J Lipid Res 48:152-64

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