title: Glia- and neuron-specific functions of TrkB signalling during retinal degeneration and regeneration.
abstract: Glia, the support cells of the central nervous system, have recently attracted considerable attention both as mediators of neural cell survival and as sources of neural regeneration. To further elucidate the role of glial and neural cells in neurodegeneration, we generated TrkB(GFAP) and TrkB(c-kit) knockout mice in which TrkB, a receptor for brain-derived neurotrophic factor (BDNF), is deleted in retinal glia or inner retinal neurons, respectively. Here, we show that the extent of glutamate-induced retinal degeneration was similar in these two mutant mice. Furthermore in TrkB(GFAP) knockout mice, BDNF did not prevent photoreceptor degeneration and failed to stimulate Müller glial cell proliferation and expression of neural markers in the degenerating retina. These results demonstrate that BDNF signalling in glia has important roles in neural protection and regeneration, particularly in conversion of Müller glia to photoreceptors. In addition, our genetic models provide a system in which glia- and neuron-specific gene functions can be tested in central nervous system tissues in vivo.
authors.affiliation: Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, Tokyo 183-8526, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Harada
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Guo
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Namekata
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kimura
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nakamura
authors.forename: Kohichi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Luis F
authors.initials: LF
authors.lastname: Parada
authors.forename: Takayuki
authors.initials: T
authors.lastname: Harada
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002478:Cells, Cultured; D018698:Glutamic Acid; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009457:Neuroglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D012162:Retinal Degeneration / Q000139:chemically induced / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology*; D001616:beta-Galactosidase
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018698:Glutamic Acid; D020813:Receptor, trkB; D001616:beta-Galactosidase