BDNF Promotes Differentiation and Maturation of Adult-born Neurons through GABAergic Transmission
| Autor: | Emily G. Waterhouse, Bai Lu, Kang Zheng, Baoji Xu, Lauren L. Orefice, Juan Ji An, Maryna Baydyuk, Guey-Ying Liao |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Brain-derived neurotrophic factor
medicine.medical_specialty General Neuroscience Dentate gyrus Neurogenesis Tropomyosin receptor kinase B Biology Neural stem cell gamma-Aminobutyric acid Subgranular zone Endocrinology medicine.anatomical_structure nervous system Internal medicine medicine GABAergic medicine.drug |
| Zdroj: | The Journal of Neuroscience. 32:14318-14330 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.0709-12.2012 |
| Popis: | Brain-derived neurotrophic factor (BDNF) has been implicated in regulating adult neurogenesis in the subgranular zone (SGZ) of the dentate gyrus; however, the mechanism underlying this regulation remains unclear. In this study, we found thatBdnfmRNA localized to distal dendrites of dentate gyrus granule cells isolated from wild-type (WT) mice, but not fromBdnfklox/kloxmice where the long 3′ untranslated region (UTR) ofBdnfmRNA is truncated. KCl-induced membrane depolarization stimulated release of dendritic BDNF translated from long 3′ UTRBdnfmRNA in cultured hippocampal neurons, but not from short 3′ UTRBdnfmRNA.Bdnfklox/kloxmice exhibited reduced expression of glutamic acid decarboxylase 65 (a GABA synthase), increased proliferation of progenitor cells, and impaired differentiation and maturation of newborn neurons in the SGZ. These deficits in adult neurogenesis were rescued with administration of phenobarbital, an enhancer of GABAAreceptor activity. Furthermore, we observed similar neurogenesis deficits in mice where the receptor for BDNF, TrkB, was selectively abolished in parvalbumin (PV)-expressing GABAergic interneurons. Thus, our data suggest that locally synthesized BDNF in dendrites of granule cells promotes differentiation and maturation of progenitor cells in the SGZ by enhancing GABA release, at least in part, from PV-expressing GABAergic interneurons. |
| Databáze: | OpenAIRE |
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