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Published in: Molecular Autism 1/2019

Open Access 01-12-2019 | Intense Pulsed Light | Research

Retinal alterations in a pre-clinical model of an autism spectrum disorder

Authors: Elisa Maria Guimarães-Souza, Christina Joselevitch, Luiz Roberto G. Britto, Silvana Chiavegatto

Published in: Molecular Autism | Issue 1/2019

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Abstract

Background

Autism spectrum disorders (ASD) affect around 1.5% of people worldwide. Symptoms start around age 2, when children fail to maintain eye contact and to develop speech and other forms of communication. Disturbances in glutamatergic and GABAergic signaling that lead to synaptic changes and alter the balance between excitation and inhibition in the developing brain are consistently found in ASD. One of the hallmarks of these disorders is hypersensitivity to sensory stimuli; however, little is known about its underlying causes. Since the retina is the part of the CNS that converts light into a neuronal signal, we set out to study how it is affected in adolescent mice prenatally exposed to valproic acid (VPA), a useful tool to study ASD endophenotypes.

Methods

Pregnant female mice received VPA (600 mg/kg, ip) or saline at gestational day 11. Their male adolescent pups (P29–35) were behaviorally tested for anxiety and social interaction. Proteins known to be related with ASD were quantified and visualized in their retinas by immunoassays, and retinal function was assessed by full-field scotopic electroretinograms (ERGs).

Results

Early adolescent mice prenatally exposed to VPA displayed impaired social interest and increased anxiety-like behaviors consistent with an ASD phenotype. The expression of GABA, GAD, synapsin-1, and FMRP proteins were reduced in their retinas, while mGluR5 was increased. The a-wave amplitudes of VPA-exposed were smaller than those of CTR animals, whereas the b-wave and oscillatory potentials were normal.

Conclusions

This study establishes that adolescent male mice of the VPA-induced ASD model have alterations in retinal function and protein expression compatible with those found in several brain areas of other autism models. These results support the view that synaptic disturbances with excitatory/inhibitory imbalance early in life are associated with ASD and point to the retina as a window to understand their subjacent mechanisms.
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Literature
6.
go back to reference Chaste P, Leboyer M. Autism risk factors: genes, environment, and gene-environment interactions. Dialogues Clin Neurosci. 2012;14(3):281–92.PubMedPubMedCentral Chaste P, Leboyer M. Autism risk factors: genes, environment, and gene-environment interactions. Dialogues Clin Neurosci. 2012;14(3):281–92.PubMedPubMedCentral
7.
go back to reference Lambert PA, Carraz G, Borselli S, Bouchardy M. Dipropylacetamide in the treatment of manic-depressive psychosis. Encephale. 1975;1(1):25–31.PubMed Lambert PA, Carraz G, Borselli S, Bouchardy M. Dipropylacetamide in the treatment of manic-depressive psychosis. Encephale. 1975;1(1):25–31.PubMed
23.
go back to reference Shimizu S. Routes of administration. In: Hedrich HJ, Bullock G, editors. The laboratory mouse. Amsterdam: Elsevier Ltd; 2004. p. 527–42.CrossRef Shimizu S. Routes of administration. In: Hedrich HJ, Bullock G, editors. The laboratory mouse. Amsterdam: Elsevier Ltd; 2004. p. 527–42.CrossRef
33.
go back to reference Saft P, Toledo-Cardenas R, Coria-Avila GA, Perez-Pouchoulen M, Brug B, Hernandez ME, et al. Characterization of four types of tail abnormalities in rats treated prenatally with valproic acid. Revista Eneurobiología. 2014;5(9):070714. Saft P, Toledo-Cardenas R, Coria-Avila GA, Perez-Pouchoulen M, Brug B, Hernandez ME, et al. Characterization of four types of tail abnormalities in rats treated prenatally with valproic acid. Revista Eneurobiología. 2014;5(9):070714.
41.
go back to reference Codagnone MG, Podestá MF, Uccelli NA, Reinés A. Differential local connectivity and neuroinflammation profiles in the medial prefrontal cortex and hippocampus in the valproic acid rat model of autism. Dev Neurosci. 2015. https://doi.org/10.1159/000375489. Codagnone MG, Podestá MF, Uccelli NA, Reinés A. Differential local connectivity and neuroinflammation profiles in the medial prefrontal cortex and hippocampus in the valproic acid rat model of autism. Dev Neurosci. 2015. https://​doi.​org/​10.​1159/​000375489.
44.
Metadata
Title
Retinal alterations in a pre-clinical model of an autism spectrum disorder
Authors
Elisa Maria Guimarães-Souza
Christina Joselevitch
Luiz Roberto G. Britto
Silvana Chiavegatto
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Molecular Autism / Issue 1/2019
Electronic ISSN: 2040-2392
DOI
https://doi.org/10.1186/s13229-019-0270-8

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