Dendritic Spine Structural Anomalies in Fragile-X Mental Retardation Syndrome

Irwin, S. A.

doi:10.1093/cercor/10.10.1038

Cited by 626Genetics and Neurodevelopmental DisordersNeuroscience and Neuropharmacology ResearchDown syndrome and intellectual disability research

Dendritic Spine Structural Anomalies in Fragile-X Mental Retardation Syndrome

Irwin, S. A.·2000·Cerebral Cortex

DOI 10.1093/cercor/10.10.1038

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Abstract

Fragile-X syndrome is the most common single-gene inherited form of mental retardation. Morphological studies suggest a possible failure of the synapse maturation process. Cerebral cortical spine morphology in fragile-X syndrome and in a knockout mouse model of it appears immature, with long, thin spines much more common than the stubby and mushroom-shaped spines more characteristic of normal development. In human fragile-X syndrome there is also a higher density of spines along dendrites, suggesting a possible failure of synapse elimination. While variously misshapen spines are characteristic of a number of mental retardation syndromes, the overabundance of spines seen in fragile-X syndrome is unusual. Taken with evidence of neurotransmitter activation of the synthesis of the fragile-X protein (FMRP) at synapses in vitro and evidence for behaviorally induced FMRP expression in vivo, and with evidence compatible with a role for FMRP in regulating the synthesis of other proteins, it is possible that FMRP serves as an 'immediate early protein' at the synapse that orchestrates aspects of synaptic development and plasticity.

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Increased spine length and density observed in human fragile X postmortem studies were replicated in Fmr1 KO mice, although differences were noted dependent on age and brain area.
“The increased spine length and density observed in human postmortem studies were replicated in Fmr1 KO mice [74, 167–169], although differences were noted dependent on age and brain area.”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [167]
Absence of FMRP in both humans and mice results in improper development of dendritic spines on cortical pyramidal neurons.
“Absence of FMRP in both humans and mice results in improper development of dendritic spines on cortical pyramidal neurons (Comery et al., 1997; Irwin et al., 2000; Irwin et al., 2001; Irwin et al., 2002).”
From Oxytocin and vasopressin systems in genetic syndromes and neurodevelopmental disorders (2014) · cites this paper as Irwin et al., 2000
In a mouse model of Fragile X syndrome, spines are more numerous.
“In a mouse model of Fragile X syndrome, spines are more numerous, and a higher percentage of them appear immature upon examination of adult fixed tissues (Comery et al., 1997; Irwin et al., 2000).”
From Spatiotemporal dynamics of dendritic spines in the living brain (2014) · cites this paper as Irwin et al., 2000
In a mouse model of Fragile X syndrome, a higher percentage of spines appear immature upon examination of adult fixed tissues.
“In a mouse model of Fragile X syndrome, spines are more numerous, and a higher percentage of them appear immature upon examination of adult fixed tissues (Comery et al., 1997; Irwin et al., 2000).”
From Spatiotemporal dynamics of dendritic spines in the living brain (2014) · cites this paper as Irwin et al., 2000

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Authors: Irwin, S. A.
Affiliations: University of Illinois Urbana-Champaign (US)
Corresponding author: Irwin, S. A.
ORCID: Irwin, S. A.
Venue: Cerebral Cortex
Publisher: Oxford University Press (OUP)
Published: 2000-10-01
Volume: 10
Issue: 10
Pages: 1038-1044
ISSN: 1047-3211 (ISSN-L)
1460-2199
DOI: 10.1093/cercor/10.10.1038
OpenAlex: W2124161234
Cited by: 626
References: 72
Citations by year: 2026: 9 · 2025: 7 · 2024: 16 · 2023: 14 · 2022: 18 · 2021: 24 · 2020: 21 · 2019: 21 · 2018: 14 · 2017: 42 · 2016: 42 · 2015: 33 · 2014: 45 · 2013: 41 · 2012: 36
FWCI: 7.97
Type: journal article
Language: en
Open access: closed
Locations: Cerebral Cortex (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5f30mh011272-03, 5r01hd037175-03)
National Institute of Mental Health (MH 11272, MH-35321)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 37175)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
Keywords: fragile X syndrome, dendritic spines, FMRP, synapse maturation, synaptic pruning, dendritic spine morphology, intellectual disability, synaptic plasticity, knockout mouse models
MeSH terms: Brain, Dendrites, Fragile X Syndrome, Humans, Intellectual Disability, Nerve Tissue Proteins, Synapses, RNA-Binding Proteins, Fragile X Messenger Ribonucleoprotein 1

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Dendritic Spine Structural Anomalies in Fragile-X Mental Retardation Syndrome

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