The principal objectives of this proposal are to elucidate the properties of axonal lipid metabolism and relate the metabolism to neuronal function. Our program is based on a dual approach: biochemical studies to detect and characterize properties of lipid metabolism at the tissue level, and complementary quantitative EM autoradiography to locate sites of synthesis and redeposition of lipids. during the current granting period we have applied these approaches to characterize axonal lipid metabolism in three model systems: (1) rodent sciatic nerves (normal and diabetic), (2) frog nerves; olfactory (nonmyelinated), optic (DNS myelin) and sciatic (PNS myelin) and (3) squid nervous system including the giant axon (axoplasm) and giant synapse. The major objective of the current proposal is to exploit the information gained from these studies toward establishing the relationships between axonal lipid metabolism and neural activity. By further characterizing changes in inositol lipid metabolism with nerve conduction impairment (experimental diabetic neuropathy) and physiological perturbation (i.e. high frequency electrical stimulation and/or potassium depolarization), we will clarify relationships between nerve function and local lipid metabolism under in vivo conditions. By studying the lipid enzymes from axoplasm (squid giant axons) and axolemma (frog olfactory nerve) in a comparative way, we can begin to understand how activities of the key axonal enzymes might be regulated in vivo. We are extending our studies to the expression of mRNAs for neuronal sodium channels and Na+,K+-ATPase, proteins which physiologically mediate nerve conduction. These studies will be a basis for determining modulatory influences of local lipid metabolism. Also, these studies will provide a framework for our applying molecular biological approaches to understanding the regulation of axon- based lipid enzymes as cDNA probes for them become available.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS013980-12
Application #
3395374
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1985-09-30
Project End
1992-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
12
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Institute for Basic Research in Dev Disabil
Department
Type
DUNS #
167205090
City
Staten Island
State
NY
Country
United States
Zip Code
10314
Gould, R M; Byrd, A L; Barbarese, E (1995) The number of Schmidt-Lanterman incisures is more than doubled in shiverer PNS myelin sheaths. J Neurocytol 24:85-98
Spivack, W D; Zhong, N; Salerno, S et al. (1993) Molecular cloning of the myelin basic proteins in the shark, Squalus acanthias, and the ray, Raja erinacia. J Neurosci Res 35:577-84
Kitagawa, K; Sinoway, M P; Yang, C et al. (1993) A proteolipid protein gene family: expression in sharks and rays and possible evolution from an ancestral gene encoding a pore-forming polypeptide. Neuron 11:433-48
Alberghina, M; Gould, R M (1992) Characterization of phospholipase A2 and acyltransferase activities in squid (Loligo pealei) axoplasm: comparison with enzyme activities in other neural tissues, axolemma and axoplasmic subfractions. Neurochem Int 21:563-71
Gould, R M; Mattingly, G (1990) Regional localization of RNA and protein metabolism in Schwann cells in vivo. J Neurocytol 19:285-301
Gould, R M; Armstrong, R (1989) Use of lead aspartate block staining in quantitative EM autoradiography of phospholipids: application to myelinating peripheral nerve. J Histochem Cytochem 37:1393-9
Toews, A D; Armstrong, R; Ray, R et al. (1988) Deposition and transfer of axonally transported phospholipids in rat sciatic nerve. J Neurosci 8:593-601
Tanaka, T; Yamaguchi, H; Kishimoto, Y et al. (1987) Lipid metabolism in various regions of squid giant nerve fiber. Biochim Biophys Acta 922:85-94
Gould, R M; Connell, F; Spivack, W (1987) Phospholipid metabolism in mouse sciatic nerve in vivo. J Neurochem 48:853-9
Gould, R M; Holshek, J; Silverman, W et al. (1987) Localization of phospholipid synthesis to Schwann cells and axons. J Neurochem 48:1121-31

Showing the most recent 10 out of 13 publications