Abstract

The rate of delivery of homovanillic acid (HVA), a metabolite of dopamine, from brain to cerebrospinal fluid (CSF) was estimated as a marker of brain dopaminergic production in healthy young and old volunteers. HVA concentrations were measured in serial aliquots of lumbar CSF from 7 young and 7 older subjects, and CSF flow rate also was measured. A model was used, based on Fick's principle, to calculate the brain HVA production. Although HVA concentrations did not differ between the two age groups, HVA delivery from brain in the elderly group was 50% less than in the younger group, consistent with other evidence of reduced dopaminergic neurotransmission with age. Our method can be used to estimate delivery rates of other brain-derived substances found in CSF.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000139-06
Application #
7130960
Study Section
(BPMS)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2005
Total Cost
Indirect Cost

  Institution

Name
Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Rapoport, Stanley I; Schapiro, Mark B; May, Conrad (2004) Reduced brain delivery of homovanillic acid to cerebrospinal fluid during human aging. Arch Neurol 61:1721-4
Buerger, Katharina; Zinkowski, Raymond; Teipel, Stefan J et al. (2003) Differentiation of geriatric major depression from Alzheimer's disease with CSF tau protein phosphorylated at threonine 231. Am J Psychiatry 160:376-9
Bosetti, Francesca; Brizzi, Francesca; Barogi, Silvia et al. (2002) Cytochrome c oxidase and mitochondrial F1F0-ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer's disease. Neurobiol Aging 23:371-6
Tendi, Elisabetta A; Bosetti, Francesca; Dasgupta, S Fenella et al. (2002) Ginkgo biloba extracts EGb 761 and bilobalide increase NADH dehydrogenase mRNA level and mitochondrial respiratory control ratio in PC12 cells. Neurochem Res 27:319-23
Buerger, Katharina; Zinkowski, Raymond; Teipel, Stefan J et al. (2002) Differential diagnosis of Alzheimer disease with cerebrospinal fluid levels of tau protein phosphorylated at threonine 231. Arch Neurol 59:1267-72
DasGupta, S F; Rapoport, S I; Gerschenson, M et al. (2001) ATP synthesis is coupled to rat liver mitochondrial RNA synthesis. Mol Cell Biochem 221:3-10
Bosetti, F; Solaini, G; Tendi, E A et al. (2001) Mitochondrial cytochrome c oxidase subunit III is selectively down-regulated by aluminum exposure in PC12S cells. Neuroreport 12:721-4
Hampel, H; Buerger, K; Kohnken, R et al. (2001) Tracking of Alzheimer's disease progression with cerebrospinal fluid tau protein phosphorylated at threonine 231. Ann Neurol 49:545-6
Rapoport, S I (2001) Advances in osmotic opening of the blood-brain barrier to enhance CNS chemotherapy. Expert Opin Investig Drugs 10:1809-18