Distinct Roles for Somatically and Dendritically Synthesized Brain-Derived Neurotrophic Factor in Morphogenesis of Dendritic Spines
Open accessAbstract
Dendritic spines undergo the processes of formation, maturation, and pruning during development. Molecular mechanisms controlling spine maturation and pruning remain largely unknown. The gene for brain-derived neurotrophic factor (BDNF) produces two pools of mRNA, with either a short or long 3' untranslated region (3' UTR). Our previous results show that short 3' UTR Bdnf mRNA is restricted to cell bodies, whereas long 3' UTR Bdnf mRNA is also trafficked to dendrites for local translation. Mutant mice lacking long 3' UTR Bdnf mRNA display normal spines at 3 weeks of age, but thinner and denser spines in adults compared to wild-type littermates. These observations suggest that BDNF translated from long 3' UTR Bdnf mRNA, likely in dendrites, is required for spine maturation and pruning. In this study, using rat hippocampal neuronal cultures, we found that knocking down long 3' UTR Bdnf mRNA blocked spine head enlargement and spine elimination, whereas overexpressing long 3' UTR Bdnf mRNA had the opposite effect. The effect of long 3' UTR Bdnf mRNA on spine head enlargement and spine elimination was diminished by a human single-nucleotide polymorphism (SNP, rs712442) in its 3' UTR that inhibited dendritic localization of Bdnf mRNA. Furthermore, we found that overexpression of either Bdnf mRNA increased spine density at earlier time points. Spine morphological alterations were associated with corresponding changes in density, size, and function of synapses. These results indicate that somatically synthesized BDNF promotes spine formation, whereas dendritically synthesized BDNF is a key regulator of spine head growth and spine pruning.
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mBDNF-TrkB-signaling pathways regulate multiple events, such as apoptosis and survival of neurons, dendritic growth, spine maturation and stabilization, development of synapses, and learning- and memory-processes-dependent synaptic plasticity.
“mBDNF-TrkB-signaling pathways regulate multiple events, such as apoptosis and survival of neurons [90,91,92], dendritic growth [93,94,95,96], spine maturation and stabilization, development of synapses [96,97,98], learning- and memory-processes-dependent synaptic plasticity [99,100].”
From Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer (2020) · cites this paper as [95]
The Introduction and Discussion report that BDNF synthesized in dendrites regulates spine maturation and pruning, and the section on corresponding synaptic changes reports effects on excitatory synapse number and size. Those findings support the spine-maturation and synapse-development portions associated with this citation. Our copy does not establish dendritic growth or spine stabilization, or identify TrkB signaling as the mechanism for these effects; the citations attached to apoptosis and learning-dependent plasticity are different references. (LLM, conf=0.86)
Experimental — accuracy not yet measuredPrimary cultures of hippocampal neurons have been used as an in vitro system to investigate formation, maturation, and pruning of dendritic spines, with spine density increasing between DIV6-10, peaking at DIV14-21, and decreasing after weeks 3 or 4.
“Primary cultures of hippocampal neurons have been used as an in vitro system to investigate the formation, maturation and pruning of dendritic spines, in which dendritic spines are formed and pruned during a developmental period similar to that in vivo in mouse brain (Orefice et al., 2013; Ko et al., 2011; Papa et al., 1995), with spine density increases between 6-10 days in vitro (DIV6-10), peaks”
From Loss of mTOR-Dependent Macroautophagy Causes Autistic-like Synaptic Pruning Deficits (2014) · cites this paper as Orefice et al., 2013
BDNF-TrkB signaling pathways regulate dendritic growth, synapse development, learning- and memory-processes-dependent synaptic plasticity, apoptosis, and survival of neurons.
“BDNF-TrkB signaling pathways regulate multiple events, such as dendritic growth, pine maturation and stabilization [41,42,43], development of synapses [44,45], learning- and memory-processes-dependent synaptic plasticity [40,46,47], apoptosis, and survival of neurons [48,49,50,51].”
From BDNF as a Promising Therapeutic Agent in Parkinson’s Disease (2020) · cites this paper as [43]
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- Authors
- Orefice, L. L., Waterhouse, E. G., Partridge, J. G., Lalchandani, R. R., Vicini, S., & Xu, B.
- Affiliations
- Georgetown University Medical Center (US)
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-07-10
- Volume
- 33
- Issue
- 28
- Pages
- 11618-11632
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3724547
- OpenAlex
- W2046866871
- Cited by
- 87
- References
- 8
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 6 · 2022: 3 · 2021: 2 · 2020: 9 · 2019: 5 · 2018: 7 · 2017: 11 · 2016: 6 · 2015: 11 · 2014: 17 · 2013: 3
- FWCI
- 6.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (F30DK084717)
- National Institute of Neurological Disorders and Stroke (R01NS050596, R01NS073930, F31NS074840, NS074840)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- brain-derived neurotrophic factor, dendritic spines, dendritic spine morphogenesis, 3' untranslated region, hippocampal neurons, synaptic density, synaptic function
- MeSH terms
- Animals, Cells, Cultured, Dendrites, Female, Hippocampus, Humans, Male, Morphogenesis, Rats, Sprague-Dawley, Brain-Derived Neurotrophic Factor, Dendritic Spines, Mice, Rats, HEK293 Cells
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