Elevated microRNA-181c and microRNA-30d levels in the enlarged amygdala of the valproic acid rat model of autism
Publication year
2015Author(s)
Number of pages
12 p.
Source
Neurobiology of Disease, 80, (2015), pp. 42-53ISSN
Publication type
Article / Letter to editor
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Organization
Cognitive Neuroscience
Neuroinformatics
Human Genetics
Molecular Animal Physiology
Journal title
Neurobiology of Disease
Volume
vol. 80
Languages used
English (eng)
Page start
p. 42
Page end
p. 53
Subject
Molecular Animal Physiology; Neuroinformatics; Radboudumc 0: Other Research DCMN: Donders Center for Medical Neuroscience; Radboudumc 13: Stress-related disorders DCMN: Donders Center for Medical Neuroscience; Radboudumc 3: Disorders of movement DCMN: Donders Center for Medical Neuroscience; Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical NeuroscienceAbstract
Autism spectrum disorders are severe neurodevelopmental disorders, marked by impairments in reciprocal social interaction, delays in early language and communication, and the presence of restrictive, repetitive and stereotyped behaviors. Accumulating evidence suggests that dysfunction of the amygdala may be partially responsible for the impairment of social behavior that is a hallmark feature of ASD. Our studies suggest that a valproic acid (VPA) rat model of ASD exhibits an enlargement of the amygdala as compared to controls rats, similar to that observed in adolescent ASD individuals. Since recent research suggests that altered neuronal development and morphology, as seen in ASD, may result from a common post-transcriptional process that is under tight regulation by microRNAs (miRs), we examined genome-wide transcriptomics expression in the amygdala of rats prenatally exposed to VPA, and detected elevated miR-181c and miR-30d expression levels as well as dysregulated expression of their cognate mRNA targets encoding proteins involved in neuronal system development. Furthermore, selective suppression of miR-181c function attenuates neurite outgrowth and branching, and results in reduced synaptic density in primary amygdalar neurons in vitro. Collectively, these results implicate the small non-coding miR-181c in neuronal morphology, and provide a framework of understanding how dysregulation of a neurodevelopmentally relevant miR in the amygdala may contribute to the pathophysiology of ASD.
This item appears in the following Collection(s)
- Academic publications [238441]
- Electronic publications [122508]
- Faculty of Medical Sciences [90373]
- Faculty of Science [34986]
- Open Access publications [97504]
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