Accession Number:

ADA399146

Title:

Anti-Excitotoxic and Antioxidant TGF-BETA Family Neurotropic Factors: In Vitro Screening Models of Motor Neuron Degeneration

Descriptive Note:

Annual rept. 1 Jun 2000-31 May 2001

Corporate Author:

JOHN HOPKINS UNIV BETHESDA MD OPERATIONS RESEARCH OFFICE

Personal Author(s):

• Rothatain, Jeffrey D.

Report Date:

2001-07-01

Pagination or Media Count:

19.0

Abstract:

TGFBeta-like trophic factors have been shown to be protective in acute neuronal injury paradigms. In the current studies, we analyzed and compared members of this growing family, including GDNF, neurturin, nodal, persephin, TGFbeta1 as well as neuroimmunophilin ligand GPI-1046, for protection against chronic glutamate toxicity and the mechanisms for protection. In parallel, we developed a novel organotypic spinal cord culture system to study the ability of these factors to promote motor axon outgrowth. Using these systems, we were able to differentiate the neuroprotective effect of the TGFbeta-like factors from their motor axon outgrowth-promoting activity. GDNF, neurturin, persephin, and nodal all protect against excitotoxic motor neuron degeneration. Low amounts of GDNF 1 ngml and high concentrations of neurturin induced vigorous motor axon outgrowth. In contrast, nodal, persephin and TGFbeta1 did not induce motor axon outgrowth. Finally, we have ascertained that the neuroprotective properties of some of these compounds GDNF and GPI-1046 may lie in their ability to induce rapidly synthesis of the glutamate transporter EAAT2.

Descriptors:

• *MOTOR NEURONS
• *NEUROTOXINS
• HIGH RATE
• DEGRADATION
• SYNTHESIS
• TOXICITY
• GLUTAMIC ACID
• IN VITRO ANALYSIS
• CONCENTRATION(COMPOSITION)
• NERVE CELLS
• WOUNDS AND INJURIES
• SALTS
• CULTURE
• SPINAL CORD
• NERVE FIBERS

Subject Categories:

• Medicine and Medical Research
• Chemical, Biological and Radiological Warfare

Distribution Statement:

APPROVED FOR PUBLIC RELEASE