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Brain-Derived Neurotrophic Factor Is Required for the Maintenance of Cortical Dendrites
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Brain-derived neurotrophic factor (BDNF) is thought to be involved in neuronal survival, migration, morphological and biochemical differentiation, and modulation of synaptic function in the CNS. In the rodent cortex, postnatal BDNF expression is initially low but subsequently increases to reach maximal levels around weaning. Thus, BDNF expression peaks at a time when both structural and functional maturation of cortical circuitry occurs. Although the function of BDNF has been probed using many approaches, its requirements during this phase of life have not previously been examined genetically. To test the in vivo requirements for BDNF during this important phase of development we generated early-onset forebrain-specific BDNF mutant mice. Although these mice undergo forebrain-restricted deletion of BDNF by Cre-mediated recombination during embryogenesis, they are healthy, and we did not detect the loss of specific cortical excitatory or inhibitory neurons. However, the neocortex of 5-week-old mice was thinner, attributable at least partly to neuronal shrinkage. Importantly, although visual cortical layer 2/3 neurons in the mutants initially developed normal dendrite structure, dendritic retraction became apparent by 3 weeks of age. Thus, our observations suggest that cortically expressed BDNF functions to support the maintenance of cortical neuron size and dendrite structure rather than the initial development of these features. This is consistent with a role for BDNF in stabilizing the "survival" of circuitry during the phase of activity-dependent reorganization of cortical connectivity.
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“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 [93]
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“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 [41]
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Metadata
- Authors
- Gorski, J. A., Zeiler, S. R., Tamowski, S., & Jones, K. R.
- Affiliations
- University of Colorado Boulder (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2003-07-30
- Volume
- 23
- Issue
- 17
- Pages
- 6856-6865
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6740724
- OpenAlex
- W2110442840
- Cited by
- 411
- References
- 79
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 13 · 2023: 13 · 2022: 9 · 2021: 13 · 2020: 16 · 2019: 12 · 2018: 25 · 2017: 16 · 2016: 21 · 2015: 28 · 2014: 28 · 2013: 20 · 2012: 30
- FWCI
- 6.92
- 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
- American Cancer Society
- Muscular Dystrophy Association
- Wellcome Trust
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- brain-derived neurotrophic factor, dendritic retraction, neocortex development, neuronal survival, neuronal shrinkage, postnatal development
- MeSH terms
- Age Factors, Animals, Behavior, Animal, Cell Count, Cell Survival, Cerebral Cortex, Dendrites, Female, Lysine, Male, Mice, Mutant Strains, Neurons, Organ Specificity, Prosencephalon, Pyramidal Cells, Gene Targeting, Gene Expression Regulation, Developmental, Brain-Derived Neurotrophic Factor, Neurodegenerative Diseases, Cell Size, Mice
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