Elevated microRNA-181c and microRNA-30d levels in the enlarged amygdala of the valproic acid rat model of autism

Abstract 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 th...

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Published in:Neurobiology of disease 2015-08, Vol.80, p.42-53
Main Authors: Olde Loohuis, N.F.M, Kole, K, Glennon, J.C, Karel, P, Van der Borg, G, Van Gemert, Y, Van den Bosch, D, Meinhardt, J, Kos, A, Shahabipour, F, Tiesinga, P, van Bokhoven, H, Martens, G.J.M, Kaplan, B.B, Homberg, J.R, Aschrafi, A
Format: Article
Language:English
Subjects:
Amygdala
Amygdala - metabolism
Amygdala - pathology
Animals
Autism spectrum disorder
Autistic Disorder - chemically induced
Autistic Disorder - genetics
Autistic Disorder - metabolism
Autistic Disorder - pathology
Disease Models, Animal
Gene networks
MicroRNA
MicroRNAs - metabolism
Neurodevelopmental disorder
Neurology
Neurons - metabolism
Neurons - pathology
Rat model of autism
Rats
Social Behavior
Transcriptome
Valproic Acid
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Summary:Abstract 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.
ISSN:0969-9961
1095-953X
DOI:10.1016/j.nbd.2015.05.006