title: GDNF facilitates differentiation of the adult dentate gyrus-derived neural precursor cells into astrocytes via STAT3.
abstract: While the pro-neurogenic actions of antidepressants in the adult hippocampal dentate gyrus (DG) are thought to be one of the mechanisms through which antidepressants exert their therapeutic actions, antidepressants do not increase proliferation of neural precursor cells derived from the adult DG. Because previous studies showed that antidepressants increase the expression and secretion of glial cell line-derived neurotrophic factor (GDNF) in C6 glioma cells derived from rat astrocytes and GDNF increases neurogenesis in adult DG in vivo, we investigated the effects of GDNF on the proliferation, differentiation and apoptosis of cultured neural precursor cells derived from the adult DG. Data showed that GDNF facilitated the differentiation of neural precursor cells into astrocytes but had no effect on their proliferation or apoptosis. Moreover, GDNF increased the phosphorylation of STAT3, and both a specific inhibitor of STAT3 and lentiviral shRNA for STAT3 decreased their differentiation into astrocytes. Taken together, our findings suggest that GDNF facilitates astrogliogenesis from neural precursor cells in adult DG through activating STAT3 and that this action might indirectly affect neurogenesis.
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan. shuboku@med.hokudai.ac.jp
authors.forename: Shuken
authors.initials: S
authors.lastname: Boku
authors.forename: Shin
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Takamura
authors.forename: Akiko
authors.initials: A
authors.lastname: Kato
authors.forename: Minoru
authors.initials: M
authors.lastname: Takebayashi
authors.forename: Kazue
authors.initials: K
authors.lastname: Hisaoka-Nakashima
authors.forename: Yuki
authors.initials: Y
authors.lastname: Omiya
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inoue
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kusumi
mesh_terms: D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D018891:Dentate Gyrus / Q000166:cytology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat