Astrocyte-Derived BDNF supports myelin protein synthesis after cuprizone-induced demyelination

Clifton G. Fulmer, Melissa W. VonDran, Althea A. Stillman, Yangyang Huang, Barbara L. Hempstead, Cheryl F. Dreyfus

Research output: Contribution to journalArticlepeer-review

105 Scopus citations


It is well established that BDNF may enhance oligodendrocyte differentiation following a demyelinating lesion, however, the endogenous sources of BDNF that may be harnessed to reverse deficits associated with such lesions are poorly defined. Here, we investigate roles of astrocytes in synthesizing and releasing BDNF. These cells are known to express BDNF following injury in vivo. In culture, they increase BDNF synthesis and release in response to glutamate metabotropic stimulation. Following cuprizone-elicited demyelination in mice, astrocytes contain BDNF and increase levels of metabotropic receptors. The metabotropic agonist, trans-(1S,3R)-1-amino-1,3- cyclopentanedicarboxylic acid (ACPD), was therefore injected into the demyelinating lesion. Increases in BDNF, as well as myelin proteins, were observed. Effects of ACPD were eliminated by coinjection of trkB-Fc to locally deplete BDNF and by deletion of astrocytederived BDNF. The data indicate that astrocyte-derived BDNF may be a source of trophic support that can be used to reverse deficits elicited following demyelination.

Original languageEnglish (US)
Pages (from-to)8186-8196
Number of pages11
JournalJournal of Neuroscience
Issue number24
StatePublished - 2014

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)


  • ACPD
  • Astrocytes
  • BDNF
  • Cuprizone
  • Metabotropic receptors
  • Oligodendrocytes


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