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Cited by 401Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersNeurogenesis and neuroplasticity mechanisms

Involvement of PGC-1α in the formation and maintenance of neuronal dendritic spines

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Cheng, Aiwu, Wan, Ruiqian, Yang, Jenq-Lin, Kamimura, Naomi, Son, Tae Gen, Ouyang, Xin, Luo, Yongquan, Okun, Eitan +1 more·2012·Nature Communications
DOI 10.1038/ncomms2238PMC PMC4091730
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Abstract

The formation, maintenance and reorganization of synapses are critical for brain development and the responses of neuronal circuits to environmental challenges. Here we describe a novel role for peroxisome proliferator-activated receptor γ co-activator 1α, a master regulator of mitochondrial biogenesis, in the formation and maintenance of dendritic spines in hippocampal neurons. In cultured hippocampal neurons, proliferator-activated receptor γ co-activator 1α overexpression increases dendritic spines and enhances the molecular differentiation of synapses, whereas knockdown of proliferator-activated receptor γ co-activator 1α inhibits spinogenesis and synaptogenesis. Proliferator-activated receptor γ co-activator 1α knockdown also reduces the density of dendritic spines in hippocampal dentate granule neurons in vivo. We further show that brain-derived neurotrophic factor stimulates proliferator-activated receptor γ co-activator-1α-dependent mitochondrial biogenesis by activating extracellular signal-regulated kinases and cyclic AMP response element-binding protein. Proliferator-activated receptor γ co-activator-1α knockdown inhibits brain-derived neurotrophic factor-induced dendritic spine formation without affecting expression and activation of the brain-derived neurotrophic factor receptor tyrosine receptor kinase B. Our findings suggest that proliferator-activated receptor γ co-activator-1α and mitochondrial biogenesis have important roles in the formation and maintenance of hippocampal dendritic spines and synapses.

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  • Maintaining the anti-inflammatory (reparative) M2 phenotype of macrophages and microglia is crucial for PGC-1α induction in penumbral neurons since the M2 phenotype is the main source of neurotrophins, which are positive modulators of PGC-1α.

    “Maintaining the anti-inflammatory (reparative) M2 phenotype of macrophages and microglia is crucial for PGC-1α induction in penumbral neurons since the M2 phenotype is the main source of neurotrophins, which are positive modulators of PGC-1α [17,90].”

    From Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis (2021) · cites this paper as [17]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

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  • The present study revealed novel effective and safe pharmacological modulators of PGC-1α, which determines increases in cellular energy production, neuron functionality, and viability.

    “The present study revealed novel effective and safe pharmacological modulators of the transcription coactivator PGC-1α, which determines increases in cellular energy production, neuron functionality, and viability [2,5,17,80].”

    From Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis (2021) · cites this paper as [17]

    The Results section (page unavailable) reports that PGC-1α overexpression raised ATP levels in cultured hippocampal neurons, and the Discussion links PGC-1α to functional synapse formation. The paper does not demonstrate that increasing PGC-1α improves neuronal viability; it discusses protection as a possibility and reports no increase in cell death after PGC-1α knockdown. The citing authors’ claim to have discovered pharmacological modulators describes their own study, not this source. (LLM, conf=0.86)

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References 64 · Cited by 401

Research works printed but not linked: 55

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Authors
Cheng, A., Wan, R., Yang, J.-L., Kamimura, N., Son, T. G., Ouyang, X., Luo, Y., Okun, E., & Mattson, M. P.
Affiliations
  • National Institute on Aging (US)
  • National Institutes of Health (US)
  • Johns Hopkins University (US)
Corresponding author
Cheng, Aiwu
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2012-12-04
Volume
3
Issue
1
Pages
1250-1250
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/ncomms2238
PMC
PMC4091730
OpenAlex
W2004632368
Cited by
401
References
64
Citations by year
2026: 22 · 2025: 32 · 2024: 42 · 2023: 26 · 2022: 38 · 2021: 48 · 2020: 34 · 2019: 22 · 2018: 34 · 2017: 26 · 2016: 23 · 2015: 25 · 2014: 20 · 2013: 8 · 2012: 1
FWCI
7.12
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • Johns Hopkins University
  • Peking University
  • National Institutes of Health
  • Japan Society for the Promotion of Science (23500971)
  • National Institute on Aging (Z01AG000317)
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 › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
PGC-1α, dendritic spines, synaptogenesis, synapse maintenance, mitochondrial biogenesis, hippocampal neurons, dentate gyrus granule cells, brain-derived neurotrophic factor, ERK signaling, CREB, TrkB, spinogenesis
MeSH terms
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Hippocampus, Mitochondria, Synapses, Transcription Factors, Up-Regulation, Polymerase Chain Reaction, RNA-Binding Proteins, Rats, Sprague-Dawley, Cyclic AMP Response Element-Binding Protein, Dentate Gyrus, Brain-Derived Neurotrophic Factor, Mitogen-Activated Protein Kinase Kinases, Dendritic Spines, Mice, Rats

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