title: Autocrine action of BDNF on dendrite development of adult-born hippocampal neurons.
abstract: Dendrite development of newborn granule cells (GCs) in the dentate gyrus of adult hippocampus is critical for their incorporation into existing hippocampal circuits, but the cellular mechanisms regulating their dendrite development remains largely unclear. In this study, we examined the function of brain-derived neurotrophic factor (BDNF), which is expressed in adult-born GCs, in regulating their dendrite morphogenesis. Using retrovirus-mediated gene transfection, we found that deletion and overexpression of BDNF in adult-born GCs resulted in the reduction and elevation of dendrite growth, respectively. This effect was mainly due to the autocrine rather than paracrine action of BDNF, because deletion of BDNF only in the newborn GCs resulted in dendrite abnormality of these neurons to a similar extent as that observed in conditional knockout (cKO) mice with BDNF deleted in the entire forebrain. Furthermore, selective expression of BDNF in adult-born GCs in BDNF cKO mice fully restored normal dendrite development. The BDNF autocrine action was also required for the development of normal density of spines and normal percentage of spines containing the postsynaptic marker PSD-95, suggesting autocrine BDNF regulation of synaptogenesis. Furthermore, increased dendrite growth of adult-born GCs caused by voluntary exercise was abolished by BDNF deletion specifically in these neurons and elevated dendrite growth due to BDNF overexpression in these neurons was prevented by reducing neuronal activity with coexpression of inward rectifier potassium channels, consistent with activity-dependent autocrine BDNF secretion. Therefore, BDNF expressed in adult-born GCs plays a critical role in dendrite development by acting as an autocrine factor.
authors.affiliation: Institute of Neuroscience, State Key Laboratory of Neuroscience and CAS Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Shanghai, China 200031.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience, State Key Laboratory of Neuroscience and CAS Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Shanghai, China 200031.
authors.forename: Xingya
authors.initials: X
authors.lastname: Chang
authors.affiliation: Institute of Neuroscience, State Key Laboratory of Neuroscience and CAS Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Shanghai, China 200031.
authors.forename: Liang
authors.initials: L
authors.lastname: She
authors.affiliation: Institute of Neuroscience, State Key Laboratory of Neuroscience and CAS Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Shanghai, China 200031.
authors.forename: Duo
authors.initials: D
authors.lastname: Xu
authors.affiliation: Institute of Neuroscience, State Key Laboratory of Neuroscience and CAS Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Shanghai, China 200031.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Institute of Neuroscience, State Key Laboratory of Neuroscience and CAS Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Shanghai, China 200031 mpoo@ion.ac.cn.
authors.forename: Mu-ming
authors.initials: MM
authors.lastname: Poo
mesh_terms: D000199:Actins / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000502:physiology*; D000076122:Disks Large Homolog 4 Protein; D000089622:Doublecortin Domain Proteins; D051528:Guanylate Kinases / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D009479:Neuropeptides / Q000378:metabolism; D014162:Transfection
chemical_list: D000199:Actins; D019208:Brain-Derived Neurotrophic Factor; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D000089622:Doublecortin Domain Proteins; C474214:Kirrel3 protein, mouse; D008164:Luminescent Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C577485:Nes protein, mouse; D064231:Nestin; D009479:Neuropeptides; D051528:Guanylate Kinases
keywords: BDNF; autocrine action; dendrite development