RT Journal Article
SR Electronic
T1 Levels of BDNF Impact Oligodendrocyte Lineage Cells following a Cuprizone Lesion
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 14182
OP 14190
DO 10.1523/JNEUROSCI.6595-10.2011
VO 31
IS 40
A1 Melissa W. VonDran
A1 Harmandeep Singh
A1 Jean Z. Honeywell
A1 Cheryl F. Dreyfus
YR 2011
UL http://www.jneurosci.org/content/31/40/14182.abstract
AB Previous work in culture has shown that basal forebrain (BF) oligodendrocyte (OLG) lineage cells respond to BDNF by increasing DNA synthesis and differentiation. Further, in the BF in vivo, reduced levels of BDNF as seen in BDNF+/− mice result in reduced numbers of NG2+ cells and deficits in myelin proteins throughout development and in the adult, suggesting that BDNF impacts the proliferating population of OLGs as well as differentiation in vivo. In this study, to investigate the roles BDNF may play in the repair of a demyelinating lesion, the cuprizone model was used and the corpus callosum was examined. BDNF protein levels were reduced after cuprizone treatment, suggesting that the demyelinating lesion itself elicits a decrease in BDNF. To analyze the effects of a further reduction of BDNF on OLG lineage cells following cuprizone, BDNF+/− mice were evaluated. These mice exhibited a blunted increase in the NG2 response at 4 and 5 weeks of cuprizone treatment. In addition, BDNF+/− mice exhibited decreased levels of myelin proteins during the demyelination and remyelination processes with no change in the total number of OLGs. These effects appear to be relatively specific to OLG lineage cells as comparable changes in CD11b+ microglia, GFAP+ astrocytes, and SMI32+ injured axons were not observed. These data indicate that BDNF may play a role following a demyelinating lesion by regulating the numbers of progenitors and the abilities of demyelinating and differentiating cells to express myelin proteins.