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Cited by 95Nerve injury and regenerationNeuroscience and Neuropharmacology ResearchNeurogenesis and neuroplasticity mechanisms

Sustained expression of brain-derived neurotrophic factor is required for maintenance of dendritic spines and normal behavior

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Vigers, A.J., Amin, D.S., Talley-Farnham, T., Gorski, J.A., Xu, B., Jones, K.R.·2012·Neuroscience
DOI 10.1016/j.neuroscience.2012.03.031PMC PMC4880414
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Abstract

Brain-derived neurotrophic factor (BDNF) plays important roles in the development, maintenance, and plasticity of the mammalian forebrain. These functions include regulation of neuronal maturation and survival, axonal and dendritic arborization, synaptic efficacy, and modulation of complex behaviors including depression and spatial learning. Although analysis of mutant mice has helped establish essential developmental functions for BDNF, its requirement in the adult is less well documented. We have studied late-onset forebrain-specific BDNF knockout (CaMK-BDNF(KO)) mice, in which BDNF is lost primarily from the cortex and hippocampus in early adulthood, well after BDNF expression has begun in these structures. We found that although CaMK-BDNF(KO) mice grew at a normal rate and can survive more than a year, they had smaller brains than wild-type siblings. The CaMK-BDNF(KO) mice had generally normal behavior in tests for ataxia and anxiety, but displayed reduced spatial learning ability in the Morris water task and increased depression in the Porsolt swim test. These behavioral deficits were very similar to those we previously described in an early-onset forebrain-specific BDNF knockout. To identify an anatomical correlate of the abnormal behavior, we quantified dendritic spines in cortical neurons. The spine density of CaMK-BDNF(KO) mice was normal at P35, but by P84, there was a 30% reduction in spine density. The strong similarities we find between early- and late-onset BDNF knockouts suggest that BDNF signaling is required continuously in the CNS for the maintenance of some forebrain circuitry also affected by developmental BDNF depletion.

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Authors
Vigers, A. J., Amin, D. S., Talley-Farnham, T., Gorski, J. A., Xu, B., & Jones, K. R.
Affiliations
  • University of Colorado Boulder (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Jones, K.R.
ORCID
Venue
Neuroscience
Publisher
Elsevier BV
Published
2012-06
Volume
212
Pages
1-18
ISSN
0306-4522 (ISSN-L)
DOI
10.1016/j.neuroscience.2012.03.031
PMC
PMC4880414
OpenAlex
W1973506089
Cited by
95
References
14
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FWCI
4.57
Type
journal article
Language
en
Open access
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Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Eye Institute (EY014998, R01EY014998)
  • National Institute of Neurological Disorders and Stroke (KO1 NS01872, P01NS016033, K01NS001872, NS-P01-16033)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
brain-derived neurotrophic factor, dendritic spines, spatial learning, depression, anxiety, ataxia, cortical neurons, hippocampus, brain size, synaptic plasticity
MeSH terms
Animals, Behavior, Animal, Mental Disorders, Cerebral Cortex, Developmental Disabilities, Disease Models, Animal, Female, Male, Mice, Transgenic, Mice, Knockout, Brain-Derived Neurotrophic Factor, Dendritic Spines, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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