title: Astrocyte-derived BDNF supports myelin protein synthesis after cuprizone-induced demyelination.
abstract: 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 astrocyte-derived 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.
authors.affiliation: Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, Graduate School of Biomedical Sciences, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, and.
authors.forename: Clifton G
authors.initials: CG
authors.lastname: Fulmer
authors.affiliation: Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, Graduate School of Biomedical Sciences, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, and.
authors.forename: Melissa W
authors.initials: MW
authors.lastname: VonDran
authors.affiliation: Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey 08854.
authors.forename: Althea A
authors.initials: AA
authors.lastname: Stillman
authors.affiliation: Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey 08854.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, New York 10065.
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Hempstead
authors.affiliation: Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, dreyfus@rwjms.rutgers.edu.
authors.forename: Cheryl F
authors.initials: CF
authors.lastname: Dreyfus
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology*; D004148:Dioxolanes / Q000494:pharmacology; D004195:Disease Models, Animal; D004965:Estrogen Antagonists / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009185:Myelin Proteins / Q000378:metabolism*; D011687:Purines / Q000494:pharmacology; D022661:RNA, Untranslated / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013629:Tamoxifen / Q000627:therapeutic use
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004148:Dioxolanes; D004965:Estrogen Antagonists; D005904:Glial Fibrillary Acidic Protein; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D009185:Myelin Proteins; D011687:Purines; D022661:RNA, Untranslated; D018094:Receptors, Metabotropic Glutamate; D013629:Tamoxifen; C104068:4-(2-amino-6-chloro-9H-purin-9-yl)-1,3-dioxolane-2-methanol; D003471:Cuprizone
keywords: ACPD; BDNF; astrocytes; cuprizone; metabotropic receptors; oligodendrocytes