Reelin signaling is impaired in autism

Fatemi, S. Hossein; Snow, Anne V.; Stary, Joel M.; Araghi-Niknam, Mohsen; Reutiman, Teri J.; Lee, Suzanne; Brooks, Andrew I.; Pearce, David A.

doi:10.1016/j.biopsych.2004.12.018

Cited by 280Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersAlzheimer's disease research and treatments

Reelin signaling is impaired in autism

Fatemi, S. Hossein, Snow, Anne V., Stary, Joel M., Araghi-Niknam, Mohsen, Reutiman, Teri J., Lee, Suzanne, Brooks, Andrew I., Pearce, David A.·2005·Biological Psychiatry

DOI 10.1016/j.biopsych.2004.12.018

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Abstract

Background Autism is a severe neurodevelopmental disorder with genetic and environmental etiologies. Recent genetic linkage studies implicate Reelin glycoprotein in causation of autism. To further investigate these studies, brain levels of Reelin protein and mRNA and mRNAs for VLDLR, Dab-1, and GSK3 were investigated.Methods Postmortem superior frontal, parietal, and cerebellar cortices of age, gender, and postmortem interval-matched autistic and control subjects were subjected to SDS-PAGE and Western blotting of Reelin protein. Quantitative reverse transcriptase polymerase chain reaction analysis of Reelin, VLDL-R, Dab-1, and GSK3 mRNA species in superior frontal and cerebellar cortices of autistic and control subjects were also performed.Results Reelin 410, 330, and 180 kDa/beta-actin values were reduced significantly in frontal and cerebellar, and nonsignificantly in parietal, areas of autistic brains versus control subjects, respectively. The mRNAs for Reln and Dab-1 were reduced significantly whereas the mRNA for Reln receptor VLDLR was elevated significantly in superior frontal and cerebellar areas of autistic brains versus control brains, respectively.Conclusions Reductions in Reelin protein and mRNA and Dab 1 mRNA and elevations in Reln receptor VLDLR mRNA demonstrate impairments in the Reelin signaling system in autism, accounting for some of the brain structural and cognitive deficits observed in the disorder.

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Altered expression of Reelin and its signaling pathways has been observed in the frontal, parietal, and cerebellar cortices of subjects with autism.
“Consistent with these findings, altered expression of Reelin and its signaling pathways has been observed in the frontal, parietal, and cerebellar cortices of subjects with autism (Fatemi et al., 2005).”
From Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity (2016) · cites this paper as Fatemi et al., 2005
Postmortem studies reveal a decrease in the expression of Reelin in schizophrenia and ASD brains as well as the cerebrospinal fluid of autistic subjects.
“Postmortem studies reveal a decrease in the expression of Reelin in schizophrenia and ASD brains as well as the cerebrospinal fluid of autistic subjects (reviewed in Refs.10, 22, and 96).”
From Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses (2017) · cites this paper as [96]
Expression of downstream signaling partners is altered in postmortem ASD brains, with reduced Dab1 expression and increased VLDLR.
“Interestingly, expression of downstream signaling partners is also altered in postmortem ASD brains, with reduced Dab1 expression and increased VLDLR (96).”
From Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses (2017) · cites this paper as [96]

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Authors: Fatemi, S. H., Snow, A. V., Stary, J. M., Araghi-Niknam, M., Reutiman, T. J., Lee, S., Brooks, A. I., & Pearce, D. A.
Affiliations: University of Minnesota (US)
University of Rochester Medicine (US)
ORCID: Fatemi, S. Hossein
Pearce, David A.
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2005-04
Volume: 57
Issue: 7
Pages: 777-787
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2004.12.018
OpenAlex: W1986579353
Cited by: 280
References: 14
Citations by year: 2026: 5 · 2025: 6 · 2024: 3 · 2023: 11 · 2022: 10 · 2021: 8 · 2020: 12 · 2019: 7 · 2018: 10 · 2017: 11 · 2016: 19 · 2015: 12 · 2014: 8 · 2013: 28 · 2012: 17
FWCI: 9.90
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords: autism spectrum disorder, reelin, Reelin signaling, VLDLR, glycogen synthase kinase-3, frontal cortex, cerebellum, postmortem brain, neurodevelopmental disorders
MeSH terms: Reelin Protein, Actins, Adult, Age Factors, Autistic Disorder, Cerebral Cortex, Female, Humans, Male, Models, Biological, Nerve Tissue Proteins, Receptors, LDL, RNA, Messenger, Serine Endopeptidases, Sex Factors, Blotting, Western, Signal Transduction, Cell Adhesion Molecules, Neuronal, Case-Control Studies, Extracellular Matrix Proteins, Reverse Transcriptase Polymerase Chain Reaction, Electrophoretic Mobility Shift Assay, Glycogen Synthase Kinase 3, Adaptor Proteins, Signal Transducing

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Reelin signaling is impaired in autism

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