Dataset Information

Hypomyelination and Oligodendroglial Alterations in a Mouse Model of Autism Spectrum Disorder.

ABSTRACT: Autism spectrum disorders (ASDs) are neuropsychiatric diseases characterized by impaired social interaction, communication deficits, and repetitive and stereotyped behaviors. ASD etiology is unknown, and both genetic and environmental causes have been proposed. Different brain structures are believed to play a role in ASD-related behaviors, including medial prefrontal cortex (mPFC), hippocampus, piriform cortex (Pir), basolateral amygdala (BLA) and Cerebellum. Compelling evidence suggests a link between white matter modifications and ASD symptoms in patients. Besides, an hypomyelination of the mPFC has been associated in rodents to social behavior impairment, one of the main symptoms of ASD. However, a comparative analysis of myelination as well as oligodendroglial (OL)-lineage cells in brain regions associated to social behaviors in animal models of ASD has not been performed so far. Here, we investigated whether OL-lineage cells and myelination are altered in a murine model of ASD induced by the prenatal exposure to valproic acid (VPA). We showed an hypomyelination in the BLA and Pir of adult VPA-exposed mice. These results were accompanied by a decrease in the number of OL-lineage cells and of mature OLs in the Pir, in addition to the mPFC, where myelination presented no alterations. In these regions the number of oligodendrocyte progenitors (OPCs) remained unaltered. Likewise, activation of histone deacetylases (HDACs) on OL-lineage cells in adulthood showed no differences. Overall, our results reveal OL-lineage cell alterations and hypomyelination as neuropathological hallmarks of ASD that have been overlooked so far.

SUBMITTER: Graciarena M

PROVIDER: S-EPMC6338056 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Hypomyelination and Oligodendroglial Alterations in a Mouse Model of Autism Spectrum Disorder.

Graciarena Mariana M Seiffe Araceli A Nait-Oumesmar Brahim B Depino Amaicha M AM

Frontiers in cellular neuroscience 20190111

Autism spectrum disorders (ASDs) are neuropsychiatric diseases characterized by impaired social interaction, communication deficits, and repetitive and stereotyped behaviors. ASD etiology is unknown, and both genetic and environmental causes have been proposed. Different brain structures are believed to play a role in ASD-related behaviors, including medial prefrontal cortex (mPFC), hippocampus, piriform cortex (Pir), basolateral amygdala (BLA) and Cerebellum. Compelling evidence suggests a link ...[more]

PMID: 30687009

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Project description:BackgroundAutism 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.MethodsPregnant 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).ResultsEarly 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.ConclusionsThis 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.

Dataset Information

Hypomyelination and Oligodendroglial Alterations in a Mouse Model of Autism Spectrum Disorder.

Publications

Hypomyelination and Oligodendroglial Alterations in a Mouse Model of Autism Spectrum Disorder.

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