Cited by 345Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersTreatment of Major Depression

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Synapse Pathology in Psychiatric and Neurologic Disease

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van Spronsen, Myrrhe, Hoogenraad, Casper C.·2010·Current Neurology and Neuroscience Reports

DOI 10.1007/s11910-010-0104-8PMC PMC2857788

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Abstract

Inhibitory and excitatory synapses play a fundamental role in information processing in the brain. Excitatory synapses usually are situated on dendritic spines, small membrane protrusions that harbor glutamate receptors and postsynaptic density components and help transmit electrical signals. In recent years, it has become evident that spine morphology is intimately linked to synapse function--smaller spines have smaller synapses and support reduced synaptic transmission. The relationship between synaptic signaling, spine shape, and brain function is never more apparent than when the brain becomes dysfunctional. Many psychiatric and neurologic disorders, ranging from mental retardation and autism to Alzheimer's disease and addiction, are accompanied by alterations in spine morphology and synapse number. In this review, we highlight the structure and molecular organization of synapses and discuss functional effects of synapse pathology in brain disease.

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Fig. 1 Molecular architecture of inhibitory and excitatory synapses. The top panels show excitatory and inhibitory synapses. Excitatory synapses target on mature mushroom-shaped spines containing a prominent postsynaptic density (PSD), and inhibitory synapses are present along the dendritic shaft lacking postsynaptic thickening. Various organelles support the synapse; mitochondria provide energy, polyribosomes and RNA particles allow local protein synthesis, recycling endosomes (REs) transport internalized synaptic receptors back to the plasma membrane, and the cytoskeleton regulates spine dynamics. The abundant actin cytoskeleton is connected to the PSD and is the primary determinant of spine shape and motility. Transient invasion of dynamic microtubule into dendritic spines can regulate formation of spine head protrusions and rapid spine growth. Excitatory and inhibitory synapses contain a unique set of channels, scaffolding proteins, and other postsynaptic molecules. The microanatomy of the inhibitory and excitatory synapses and their organization of proteins and protein–protein interactions are depicted in the left and right panels, respectively. Major families of postsynaptic proteins are shown, including scaffolding proteins, adhesion molecules, and receptors. The lower panel shows major morphologic events occurring in dendritic spines upon long-term potentiation (LTP; left) or long-term depression (LTD; right). In Alzheimer’s disease and mental retardation, signaling cascades are triggered similar to LTD, leading to thinner, immature spines. In contrast, cocaine addiction shows similarities to LTP, resulting in bigger, mushroom-shaped, mature spines. The molecular and morphologic changes in the synapse are hallmarks of the disease pathology and are responsible for the cognitive alterations in neuropsychiatric diseases. CamKII—Ca2+/calmodulin-dependent kinase II; AMPAR—amino-3-hydroxy-5-methyl-4-isoazolepropionate receptor; GABA—γ-aminobutyric acid; GABAR—GABA receptor; NMDAR—N-methyl-d-aspartate receptor; mGluR—metabotropic glutamate receptor; SAPAP—synapse-associated protein 90/PSD-95-associated proteinCC BY-NC · PubMed Central

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THE SYNAPTIC VESICLE CYCLE
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Experience-dependent structural synaptic plasticity in the mammalian brain
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Neuroligins and neurexins link synaptic function to cognitive disease
Südhof, T. C. (2008) · Nature · doi:10.1038/nature07456 · Cited by 1,849
Amyloid-β Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle
Kang, J.-E., Lim, M. M., Bateman, R. J., Lee, J. J., Smyth, L. P., Cirrito, J. R., Fujiki, N., Nishino, S., & Holtzman, D. M. (2009) · Science · doi:10.1126/science.1180962 · Cited by 1,565
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Morphological Changes in Dendritic Spines Associated with Long-Term Synaptic Plasticity
Yuste, R., & Bonhoeffer, T. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1071 · Cited by 1,269
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Lau, C. G., & Zukin, R. S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2153 · Cited by 1,159 · cited 1×
“Moreover, alterations in synaptic receptor trafficking, abnormal spine morphology, and defects in synaptic function have been reported in animal models of neuropsychiatric disorders including addiction and schizophrenia [8, 34 ], as well as in models of mental retardation, such as FXS [35].”
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Hsieh, H., Boehm, J., Sato, C., Iwatsubo, T., Tomita, T., Sisodia, S., & Malinow, R. (2006) · Neuron · doi:10.1016/j.neuron.2006.10.035 · Cited by 1,042
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Wang, K., Zhang, H., Ma, D., Bucan, M., Glessner, J. T., Abrahams, B. S., Salyakina, D., Imielinski, M., Bradfield, J. P., Sleiman, P. M. A., et al. (2009) · Nature · doi:10.1038/nature07999 · Cited by 989
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Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice
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Structure-stability-function relationships of dendritic spines
Kasai, H., Matsuzaki, M., Noguchi, J., Yasumatsu, N., & Nakahara, H. (2003) · Trends in Neurosciences · doi:10.1016/s0166-2236(03)00162-0 · Cited by 847
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Stephan, K. E., Baldeweg, T., & Friston, K. J. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.10.005 · Cited by 841
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Götz, J., & Ittner, L. M. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2420 · Cited by 676
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Authors: van Spronsen, M., & Hoogenraad, C. C.
Affiliations: Erasmus MC (NL)
Corresponding author: Hoogenraad, Casper C.
ORCID: Hoogenraad, Casper C.
Venue: Current Neurology and Neuroscience Reports
Publisher: Springer Science and Business Media LLC
Published: 2010-03-18
Volume: 10
Issue: 3
Pages: 207-214
ISSN: 1528-4042 (ISSN-L)
1534-6293
DOI: 10.1007/s11910-010-0104-8
PMC: PMC2857788
OpenAlex: W2098229885
Cited by: 345
References: 50
Citations by year: 2026: 5 · 2025: 14 · 2024: 13 · 2023: 16 · 2022: 22 · 2021: 18 · 2020: 21 · 2019: 20 · 2018: 29 · 2017: 21 · 2016: 25 · 2015: 26 · 2014: 22 · 2013: 24 · 2012: 38
FWCI: 2.66
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
Locations: Current Neurology and Neuroscience Reports (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
RePub (Erasmus University Rotterdam) (submittedVersion)
Funders: ZonMw
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
Keywords: dendritic spines, dendritic spine morphology, excitatory synapses, inhibitory synapses, synaptic transmission, postsynaptic density, glutamate receptors, mental illness, neurological disorders, autism spectrum disorder, intellectual disability, Alzheimer's disease, addiction, synapse number
MeSH terms: Mental Disorders, Humans, Models, Biological, Nervous System Diseases, Neuronal Plasticity, Neurons, Synapses, Dendritic Spines

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