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Molecular Autism
Published in: Molecular Autism 1/2015

Open Access 01-12-2015 | Research

Ultrastructural analyses in the hippocampus CA1 field in Shank3-deficient mice

Authors: Neha Uppal, Rishi Puri, Frank Yuk, William G M Janssen, Ozlem Bozdagi-Gunal, Hala Harony-Nicolas, Dara L Dickstein, Joseph D Buxbaum, Patrick R Hof

Published in: Molecular Autism | Issue 1/2015

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Abstract

Background

The genetics of autism spectrum disorder (hereafter referred to as “autism”) are rapidly unfolding, with a significant increase in the identification of genes implicated in the disorder. Many of these genes are part of a complex landscape of genetic variants that are thought to act together to cause the behavioral phenotype associated with autism. One of the few single-locus causes of autism involves a mutation in the SH3 and multiple ankyrin repeat domains 3 (SHANK3) gene. Previous electrophysiological studies in mice with Shank3 mutations demonstrated impairment in synaptic long-term potentiation, suggesting a potential disruption at the synapse.

Methods

To understand how variants in SHANK3 would lead to such impairments and manifest in the brain of patients with autism, we assessed the presence of synaptic pathology in Shank3-deficient mice at 5 weeks and 3 months of age, focusing on the stratum radiatum of the CA1 field. This study analyzed both Shank3 heterozygous and homozygous mice using an electron microscopy approach to determine whether there is a morphological correlate to the synaptic functional impairment.

Results

As both synaptic strength and plasticity are affected in Shank3-deficient mice, we hypothesized that there would be a reduction in synapse density, postsynaptic density length, and perforated synapse density. No differences were found in most parameters assessed. However, Shank3 heterozygotes had significantly higher numbers of perforated synapses at 5 weeks compared to 3 months of age and significantly higher numbers of perforated synapses compared to 5-week-old wildtype and Shank3 homozygous mice.

Conclusions

Although this finding represents preliminary evidence for ultrastructural alterations, it suggests that while major structural changes seem to be compensated for in Shank3-deficient mice, more subtle morphological alterations, affecting synaptic structure, may take place in an age-dependent manner.
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Metadata
Title
Ultrastructural analyses in the hippocampus CA1 field in Shank3-deficient mice
Authors
Neha Uppal
Rishi Puri
Frank Yuk
William G M Janssen
Ozlem Bozdagi-Gunal
Hala Harony-Nicolas
Dara L Dickstein
Joseph D Buxbaum
Patrick R Hof
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2015
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/s13229-015-0036-x

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