Cited by 125Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersNeural dynamics and brain function

Developmental vulnerability of synapses and circuits associated with neuropsychiatric disorders

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Penzes, Peter, Buonanno, Andres, Passafaro, Maria, Sala, Carlo, Sweet, Robert A.·2013·Journal of Neurochemistry

Abstract

Psychiatric and neurodegenerative disorders, including intellectual disability, autism spectrum disorders (ASD), schizophrenia (SZ), and Alzheimer's disease, pose an immense burden to society. Symptoms of these disorders become manifest at different stages of life: early childhood, adolescence, and late adulthood, respectively. Progress has been made in recent years toward understanding the genetic substrates, cellular mechanisms, brain circuits, and endophenotypes of these disorders. Multiple lines of evidence implicate excitatory and inhibitory synaptic circuits in the cortex and hippocampus as key cellular substrates of pathogenesis in these disorders. Excitatory/inhibitory balance – modulated largely by dopamine – critically regulates cortical network function, neural network activity (i.e. gamma oscillations) and behaviors associated with psychiatric disorders. Understanding the molecular underpinnings of synaptic pathology and neuronal network activity may thus provide essential insight into the pathogenesis of these disorders and can reveal novel drug targets to treat them. Here, we discuss recent genetic, neuropathological, and molecular studies that implicate alterations in excitatory and inhibitory synaptic circuits in the pathogenesis of psychiatric disorders across the lifespan.

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Crossref · 10.1111/jnc.12261

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  • Evidence for ECM/PNN pathology in psychiatric disorders supports the hypothesis that ECM/PNN abnormalities may contribute to a critical pathological component shared by psychiatric disorders, i.e., disruption of synaptic functions.

    “Evolving in parallel with our understanding of these functions, evidence for ECM/PNN pathology in psychiatric disorders supports the intriguing hypothesis that ECM/PNN abnormalities may contribute to a critical pathological component shared by psychiatric disorders, i.e., disruption of synaptic functions (e.g.Penzes et al., 2013;Duman, 2014;Xu et al., 2014).”

    From Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity (2016) · cites this paper as Penzes et al., 2013

    The Introduction and Conclusions (page numbers unavailable) describe disrupted synaptic function as a potential shared feature of several psychiatric disorders. They do not link that disruption to ECM/PNN pathology or abnormalities, so the ECM/PNN-specific hypothesis is not supported by this source. (LLM, conf=0.85)

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Authors
Penzes, P., Buonanno, A., Passafaro, M., Sala, C., & Sweet, R. A.
Affiliations
  • Northwestern University (US)
  • Section on Molecular Neurobiology Eunice Shriver Kennedy NICHD National Institutes of Health Program of Developmental Neurobiology Bethesda Maryland USA
  • University of Milan (IT)
  • University of Pittsburgh (US)
Corresponding author
Penzes, Peter
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2013-05-22
Volume
126
Issue
2
Pages
165-182
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
OpenAlex
W2031695523
Cited by
125
References
216
Citations by year
2026: 5 · 2025: 5 · 2024: 8 · 2023: 4 · 2022: 7 · 2021: 11 · 2020: 11 · 2019: 3 · 2018: 13 · 2017: 10 · 2016: 17 · 2015: 15 · 2014: 11 · 2013: 5
FWCI
1.63
Type
journal article
Language
en
Open access
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Veterans Affairs (I01 BX000452)
  • Istituto Italiano di Tecnologia
  • National Institutes of Health (MH 071316, MH071533)
  • National Institute on Aging (AG027224, R01AG027224)
  • National Institute of Mental Health (MH071533, MH 071316, MH097216, R01MH097216, R01MH071533, R56MH071316, R01MH071316)
  • National Institute of Child Health and Human Development
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 › Cognitive Neuroscience › Neural dynamics and brain function
Keywords
neuropsychiatric disorders, intellectual disability, autism spectrum disorder, schizophrenia, Alzheimer's disease, excitation-inhibition balance, synaptic circuits, dopamine, gamma oscillations, hippocampus, developmental vulnerability, neuropathology, therapeutic target
MeSH terms
Animals, Mental Disorders, Brain, Humans, Nerve Net, Nervous System Diseases, Synapses

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