Abstract

The brain is a highly differentiated organ which is particularly sensitive to the lack of oxygen and glucose. The neuronal synapse (both in situ and as isolated synaptosomes) has been chosen for this study because of its key in neurotransmission and its high metabolic requirement for oxygen. The behavior of the neuronal synapse in situ will be measured on the giant synapse of animals such as the larvae of Xenopus laevis using microelectrodes. These measurements will be compared with those on isolated rat brain synaptosomes (using other methods) under various conditions, including hypoxia, in order to ascertain the physiological relevance of the properties of isolated synaptosomes to the synapse in vivo. The isolated synaptosomes will be used to study: 1. The regulation of neuronal energy metabolism with special attention to the role of mitochondrial respiration. 2. Neurotransmitter uptake and metabolism and its relation to transmembrane electrical and pH gradients. 3. The oxygen dependence of the energy metabolism and its relation to the sensitivity of the brain to hypoxia.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS014505-08
Application #
3395585
Study Section
Physical Biochemistry Study Section (PB)
Project Start
1978-04-01
Project End
1987-01-31
Budget Start
1985-07-01
Budget End
1987-01-31
Support Year
8
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Erecinska, M; Troeger, M B; Wilson, D F et al. (1986) The role of glial cells in regulation of neurotransmitter amino acids in the external environment. II. Mechanism of aspartate transport. Brain Res 369:203-14
Wilson, D F; Pastuszko, A (1986) Transport of cysteate by synaptosomes isolated from rat brain: evidence that it utilizes the same transporter as aspartate, glutamate, and cysteine sulfinate. J Neurochem 47:1091-7
Pastuszko, A; Erecinska, M; Wilson, D F et al. (1985) Some effects of ischaemia and hyperglycaemia on neurotransmitter metabolism in rat brain. Neurol Res 7:120-8
Pastuszko, A; Wilson, D F (1985) Kainate-induced uptake of calcium by synaptosomes from rat brain. FEBS Lett 192:61-5
Pastuszko, A; Wilson, D F; Erecinska, M (1985) Activation of tyrosine hydroxylase in the central nervous system by anaerobiosis. Biochem Pharmacol 34:2975-82
Hauptmann, M; Wilson, D F; Erecinska, M (1985) Effects of ATP gamma S in isolated rat brain synaptosomes. Biochem Pharmacol 34:1247-54