title: Levels of BDNF impact oligodendrocyte lineage cells following a cuprizone lesion.
abstract: 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.
authors: Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
authors: Melissa W
authors: MW
authors: VonDran
authors: Harmandeep
authors: H
authors: Singh
authors: Jean Z
authors: JZ
authors: Honeywell
authors: Cheryl F
authors: CF
authors: Dreyfus
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D002452:Cell Count; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000633:toxicity; D003337:Corpus Callosum / Q000187:drug effects / Q000378:metabolism; D003471:Cuprizone / Q000633:toxicity*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009185:Myelin Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002614:Chelating Agents; D009185:Myelin Proteins; D003471:Cuprizone