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Developmental Biology - microRNA

The Role of microRNAs in Social Behavior

Researchers uncover how one microRNA cluster regulates synapse development in mice and may also affect humans...

The discovery that microRNAs are key regulators of biological processes, has fueled an explosion of research into their function. Double stranded DNA cannot fit through the pours of a cell nucleus, so it must be unwound and copied into single strands of RNA, called messenger RNA or mRNA.

Now, a microRNA cluster just uncovered appears to control synapses that affect social behavior in mice. Researchers hope their discovery of this microRNA will lead to new strategies for treating social deficits in disorders such as autism or schizophrenia. Their research is published in EMBO Reports.
MicroRNAs are short snippets of RNA that do not code for a protein. Rather, they regulate protein stability or its translation rate — by inhibiting production of specific proteins.

microRNAs appear to form a whole layer of gene regulation only recognized in the past 15 years. Each microRNA typically targets hundreds of different mRNAs, which makes them ideal for coordinating complex cell processes.

The research group of Gerhard Schratt PhD, Institute of Physiological Chemistry, Philipps-University Marburg, Germany, along with laboratories at the Universities of Heidelberg, and the Swiss Federal Institute of Technology, Switzerland, has uncovered a cluster of 38 microRNAs, called (miR379-410), that play an important role in nerve cell development. Many indications suggest this cluster specifically targets nuerons affecting social behavior. Schratt and colleagues made their discovery in the brains of mice.
Researchers observed that mice without a functional miR379-410 complex are more sociable than their littermates. This indicates that miR379-410 restricts sociability in healthy animals. Neurons in the hippocampus of mice without miR379-410 form more connections, thus are likely to transmit more electrical signals and behave more socially.

According to Gerhard Schratt PhD, Institute of Physiological Chemistry, Philipps-University Marburg, Marburg, Germany: "Our study indicates that miR379-410 plays an important role in the development of neural circuits that control social behavior."

The miR379-410 complex targets thousands of genes at the molecular level, many known to regulate synapse transmission. Moreover, a small subgroup of only five miRNAs in that cluster might explain an increase in certain key synapse proteins. These proteins are involved in equalizing synapse responses - a feedback loop that kicks in when the brain becomes overactive if synaptic contacts are too strong.

While the current study only uses mice as a model organism, there are indications that the miR379-410 complex is also involved in regulation of social behavior in humans. For example, several miR-379-410 complex members are dysregulated (impaired) in the blood and brain of patients with neurodevelopmental disorders such as schizophrenia or autism spectrum disorders, thus affecting their social interactions.
"We hope that our study will contribute to the development of treatments to ameliorate social deficits in neuropsychiatric conditions in the future."

Gerhard Schratt PhD

Aberrant synaptic function is thought to underlie social deficits in neurodevelopmental disorders such as autism and schizophrenia. Although microRNAs have been shown to regulate synapse development and plasticity, their potential involvement in the control of social behaviour in mammals remains unexplored. Here, we show that deletion of the placental mammal-specific miR379-410 cluster in mice leads to hypersocial behaviour, which is accompanied by increased excitatory synaptic transmission, and exaggerated expression of ionotropic glutamate receptor complexes in the hippocampus. Bioinformatic analyses further allowed us to identify five “hub” microRNAs whose deletion accounts largely for the upregulation of excitatory synaptic genes observed, including Cnih2, Dlgap3, Prr7 and Src. Thus, the miR379-410 cluster acts a natural brake for sociability, and interfering with specific members of this cluster could represent a therapeutic strategy for the treatment of social deficits in neurodevelopmental disorders.

A placental mammal-specific microRNA cluster regulates sociability in mice. Loss of specific miR379-410 members leads to hypersocial behaviour in mice and enhances synaptic transmission in the hippocampus, suggesting an “anti-autistic” function of the cluster.

• Mice with a constitutive miR379-410 knockout display enhanced sociability and anxiety.

• KO of miR379-410 leads to increased spine density, excitatory synaptic transmission and ionotropic glutamate receptor expression.

• Deletion of five “hub” miRNAs from miR379-410 leads to the upregulation of synaptic genes.

• Interfering with these miRNAs might ameliorate social deficits in neuropsychiatric conditions.

Martin Lackinger, A Özge Sungur, Reetu Daswani, Michael Soutschek, Silvia Bicker, Lea Stemmler, Tatjana Wüst, Roberto Fiore, Christoph Dieterich, Rainer KW Schwarting, Markus Wöhr and Gerhard Schratt.

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Dec 18, 2018   Fetal Timeline   Maternal Timeline   News   News Archive

A placental mammal-specific microRNA cluster regulates sociability in mice. Loss of specific miR379-410 members leads to hypersocial behavior in mice and enhances synaptic transmission in the hippocampus, suggesting an “anti-autistic” function of the cluster. Image: EMBO Reports.

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