BDNF promotes differentiation and maturation of adult-born neurons through GABAergic transmission
Open accessAbstract
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 that Bdnf mRNA localized to distal dendrites of dentate gyrus granule cells isolated from wild-type (WT) mice, but not from Bdnf klox/kloxmice where the long 3′ untranslated region (UTR) of Bdnf mRNA is truncated. KCl-induced membrane depolarization stimulated release of dendritic BDNF translated from long 3′ UTR Bdnf mRNA in cultured hippocampal neurons, but not from short 3′ UTR Bdnf mRNA.Bdnf klox/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 GABA A receptor 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.
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Fluoxetine induces the expression of BDNF in dentate gyrus cells, where it exerts a marked influence on their maturation.
“This pro-differentiation effect is also in line with the finding that fluoxetine induces the expression of BDNF in dentate gyrus cells, where it exerts a marked influence on their maturation (Molteni et al., 2006;Waterhouse et al., 2012).”
From Depression and adult neurogenesis: Positive effects of the antidepressant fluoxetine and of physical exercise (2018) · cites this paper as Waterhouse et al., 2012
The Results section reports impaired maturation of newborn dentate gyrus neurons when dendritic BDNF is disrupted, supporting the claim that BDNF influences their maturation. The paper does not establish the other part of the attributed finding—that fluoxetine induces BDNF expression in dentate gyrus cells. (LLM, conf=0.85)
Experimental — accuracy not yet measuredLow brain levels of brain-derived neurotrophic factor may affect neuronal viability in major depressive disorder because BDNF supports neuronal maturation, differentiation, and neuroprotection.
“Given its role in neuronal maturation and differentiation75 as well as its neuroprotective effects76, low brain levels of BDNF may affect neuronal viability in MDD.”
From Dysregulation of adult hippocampal neuroplasticity in major depression: Pathogenesis and therapeutic implications (2022) · cites this paper as [75]
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- Authors
- Waterhouse, E. G., An, J. J., Orefice, L. L., Baydyuk, M., Liao, G.-Y., Zheng, K., Lu, B., & Xu, B.
- Affiliations
- Georgetown University Medical Center (US)
- National Institutes of Health (US)
- Corresponding author
- Xu, Baoji
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-10-10
- Volume
- 32
- Issue
- 41
- Pages
- 14318-14330
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3519245
- OpenAlex
- W2078740239
- Semantic Scholar
- ce3e7c65581cab9f49ea1a13449900624203c10e
- Cited by
- 287
- References
- 54
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 15 · 2023: 16 · 2022: 21 · 2021: 26 · 2020: 26 · 2019: 14 · 2018: 27 · 2017: 17 · 2016: 32 · 2015: 25 · 2014: 23 · 2013: 21
- FWCI
- 7.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (F30DK084717)
- National Institute of Neurological Disorders and Stroke (R56NS050596, R01NS050596, R01NS073930, F31NS074840)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- brain-derived neurotrophic factor, adult neurogenesis, dentate gyrus subgranular zone, GABAergic interneurons, parvalbumin, 3' untranslated region, GAD65, GABA release, GABAA receptor, TrkB, phenobarbital
- MeSH terms
- Age Factors, Animals, Cell Differentiation, Cells, Cultured, Female, gamma-Aminobutyric Acid, Hippocampus, Male, Mice, Inbred C57BL, Mice, Transgenic, Synaptic Transmission, Up-Regulation, Rats, Sprague-Dawley, Mice, Knockout, Brain-Derived Neurotrophic Factor, Mice, Rats, Neurogenesis, Neural Stem Cells
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