Intracellular kinetics of high energy phosphates (HEP) is of fundamental importance in cellular biochemical physiology. In mammalian brain, intracellular HEP transport from the production site (mitochondria) to the consumption site (plasma membrane) is dependent on passive diffusion of HEP through the cytosol. Diffusivity of a substrate in a solution correlates inversely to the viscosity of the solution. The maturational process of mammalian brain involves dramatic changes in the cytosolic amino acid profile. Since the viscosity of a solution is a function of the diffusion coefficients of solutes and their concentrations, changes in the cytosolic amino acid composition should result in significant alteration in cytosol viscosity and, hence, HEP diffusivity. Nevertheless, to date, little is known regarding the effect of maturational changes in cytosol composition on the diffusivity of HEP or intracellular HEP kinetics. Using in vivo nuclear magnetic resonance (NMR) diffusion spectroscopy and saturation transfer experiments, the investigators have recently demonstrated that diffusivity of HEP in rat brain indeed exhibits significant changes during the postnatal maturational period. This proposal aims to further investigate HEP diffusivity and kinetics in vivo and in vitro as a function of maturation. Studies are designed to provide a correlation between maturational changes in the cytosolic amino acid profile and HEP diffusivity, and to elucidate the maturational changes in HEP kinetics. A mathematical model of HEP diffusion is presented. The role of N-acetyl-aspartate, an amino acid present in high concentrations in adult of N-acetyl-aspartate, an amino acid present in high concentrations in adult brain and the function of which remains elusive, is expected to be clarified.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM037197-05
Application #
2178713
Study Section
Neurology A Study Section (NEUA)
Project Start
1986-07-01
Project End
1995-11-30
Budget Start
1993-12-01
Budget End
1994-11-30
Support Year
5
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of California Davis
Department
Neurology
Type
Schools of Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Nakada, T; Nakayama, N; Fujii, Y et al. (1999) Clinical application of three-dimensional anisotropy contrast magnetic resonance axonography. Technical note. J Neurosurg 90:791-5
Fujii, Y; Nakayama, N; Nakada, T (1998) High-resolution T2-reversed magnetic resonance imaging on a high magnetic field system. Technical note. J Neurosurg 89:492-5
Kwee, I L; Igarashi, H; Nakada, T (1996) Aldose reductase and sorbitol dehydrogenase activities in diabetic brain: in vivo kinetic studies using 19F 3-FDG NMR in rats. Neuroreport 7:726-8
Matsuzawa, H; Nakada, T (1996) Modified van Vaals-Bergman coaxial cable coil (lambda coil) for high-field imaging. MAGMA 4:3-6
Matsuzawa, H; Kwee, I L; Nakada, T (1995) Magnetic resonance axonography of the rat spinal cord: postmortem effects. J Neurosurg 83:1023-8
Igarashi, H; Kwee, I L; Nakada, T (1995) Guanidinoethane sulfate is neuroprotective towards delayed CA1 neuronal death in gerbils. Life Sci 56:1201-6
Nakada, T; Matsuzawa, H (1995) Three-dimensional anisotropy contrast magnetic resonance imaging of the rat nervous system: MR axonography. Neurosci Res 22:389-98
Nakada, T; Kwee, I L; Igarashi, H (1994) Brain maturation and high-energy phosphate diffusivity: alteration in cytosolic microenvironment and effective viscosity. Brain Res Dev Brain Res 80:121-6
Kamada, K; Houkin, K; Hida, K et al. (1994) Localized proton spectroscopy of focal brain pathology in humans: significant effects of edema on spin-spin relaxation time. Magn Reson Med 31:537-40
Nakada, T; Kwee, I L (1993) Guanidinoethane sulfate: brain pH alkaline shifter. Neuroreport 4:1035-8

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