Retinal alterations in a pre-clinical model of an autism spectrum disorder
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 chan...
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doaj-bc5e63e50228461d943a0b28a64e1ae02020-11-25T02:07:51ZengBMCMolecular Autism2040-23922019-04-0110111610.1186/s13229-019-0270-8Retinal alterations in a pre-clinical model of an autism spectrum disorderElisa Maria Guimarães-Souza0Christina Joselevitch1Luiz Roberto G. Britto2Silvana Chiavegatto3Department of Physiology and Biophysics, Biomedical Sciences Institute, University of São PauloDepartment of Experimental Psychology, Psychology Institute, University of São PauloDepartment of Physiology and Biophysics, Biomedical Sciences Institute, University of São PauloDepartment of Pharmacology, Biomedical Sciences Institute, University of São PauloAbstract 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.http://link.springer.com/article/10.1186/s13229-019-0270-8AutismVisionRetinaGlutamateGABAValproate |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elisa Maria Guimarães-Souza Christina Joselevitch Luiz Roberto G. Britto Silvana Chiavegatto |
spellingShingle |
Elisa Maria Guimarães-Souza Christina Joselevitch Luiz Roberto G. Britto Silvana Chiavegatto Retinal alterations in a pre-clinical model of an autism spectrum disorder Molecular Autism Autism Vision Retina Glutamate GABA Valproate |
author_facet |
Elisa Maria Guimarães-Souza Christina Joselevitch Luiz Roberto G. Britto Silvana Chiavegatto |
author_sort |
Elisa Maria Guimarães-Souza |
title |
Retinal alterations in a pre-clinical model of an autism spectrum disorder |
title_short |
Retinal alterations in a pre-clinical model of an autism spectrum disorder |
title_full |
Retinal alterations in a pre-clinical model of an autism spectrum disorder |
title_fullStr |
Retinal alterations in a pre-clinical model of an autism spectrum disorder |
title_full_unstemmed |
Retinal alterations in a pre-clinical model of an autism spectrum disorder |
title_sort |
retinal alterations in a pre-clinical model of an autism spectrum disorder |
publisher |
BMC |
series |
Molecular Autism |
issn |
2040-2392 |
publishDate |
2019-04-01 |
description |
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. |
topic |
Autism Vision Retina Glutamate GABA Valproate |
url |
http://link.springer.com/article/10.1186/s13229-019-0270-8 |
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