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The Journal of Neuroscience, July 2, 2003, 23(13):5846-5853

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The Trophic Role of Oligodendrocytes in the Basal Forebrain

Xudong Dai,1 Lauren D. Lercher,1 Patricia M. Clinton,1 Yangzhou Du,1 Denise L. Livingston,1 Cristina Vieira,1 Lu Yang,2 Michael M. Shen,2 and Cheryl F. Dreyfus1

1Department of Neuroscience and Cell Biology and 2Center for Advanced Biotechnology and Medicine and Department of Pediatrics, University of Medicine and Dentistry of New Jersey–Robert Wood Johnson Medical School, Piscataway, New Jersey 08854

Traditionally, the primary function of oligodendrocytes (OLGs) in the CNS has been considered to be myelination. Here, we investigated whether OLGs may play a trophic role, particularly during development. Neurotrophin expression was assessed in postnatal day 7 basal forebrain (BF) OLGs, using in situ hybridization and detection of myelin basic protein. Nerve growth factor, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) mRNAs were revealed in OLGs in vivo and in culture. To determine whether OLGs support nearby neurons, we examined the influence of OLGs on BF cholinergic neurons. Neuronal function was enhanced by cocultured OLGs and OLG conditioned medium. Moreover, trophic effects of OLG conditioned medium were partially blocked by K252a, a trk tyrosine kinase inhibitor, and by neutralizing anti-BDNF or anti-NT-3 antisera, indicating that neurotrophins may mediate these effects, perhaps in concert with other signals. Our studies support a novel role for OLGs in providing local trophic support for neurons in the CNS.

Key words: oligodendrocytes; basal forebrain; NGF; BDNF; NT-3; trophic role of oligodendrocytes on cholinergic neurons

Received Oct. 22, 2002; revised Apr. 24, 2003; accepted Apr. 28, 2003.






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