Previous results from our laboratory support the idea that the transcription factor CREB plays important roles as a mediator of neuroligands and growth factor signals in developing oligodendrocytes (OLGs). Moreover, we have recently observed that CREB phosphorylation is highly stimulated by the lipid bioactive molecule, sphingosine-1-phosphate (S1P). These results are crucial since they represent one of the first reports directly relating S1P with a transcription factor and could, therefore, allude to a novel mechanism of gene regulation in OLGs. Thus, in the proposed study we will focus on investigating (1) the developmental expression and identification of signaling pathways mediating the S1P-dependent stimulation of CREB phosphorylation, (2) the role of S1P in OLG development, and (3) the importance of S1P as a mediator of neurotrophin-3 actions in OLGs. A better understanding of the signaling pathways involved in OLG development will offer new avenues for the treatment of demyelinating conditions such as multiple sclerosis

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31NS048733-01A1
Application #
6884203
Study Section
Special Emphasis Panel (ZRG1-F03A (20))
Program Officer
Utz, Ursula
Project Start
2004-09-18
Project End
2005-09-17
Budget Start
2004-09-18
Budget End
2005-09-17
Support Year
1
Fiscal Year
2004
Total Cost
$29,130
Indirect Cost
Name
Virginia Commonwealth University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
Saini, Harsimran S; Coelho, Rochelle P; Goparaju, Sravan K et al. (2005) Novel role of sphingosine kinase 1 as a mediator of neurotrophin-3 action in oligodendrocyte progenitors. J Neurochem 95:1298-310