Brain mechanism underlying the evolution of anxiety

Summary: The VMAT1 gene evolved by natural selection in human evolution. Those with the Ile type variant of the VMAT1 gene are less prone to anxiety and depression.

Source: Tohoku University

Monoamine neurotransmitters such as serotonin and dopamine play an important role in our cognitive and emotional functions. Their evolutionary origins can be traced back to metazoans, and although the function of related genes is highly conserved through evolution, genetic variation within and between species has been reported to significantly impact the mental characteristics of animals such as as sociality, aggression, anxiety and depression.

A research group led by Dr. Daiki Sato and Professor Masakado Kawata previously reported that the vesicular monoamine transporter 1 (VMAT1) gene, which transports neurotransmitters to the secretory vesicles of neurons and secretory cells, evolved through natural selection during human evolution.

In particular, the 136th amino acid locus of this gene evolved in the human line from asparagine (Asn) to threonine (Thr), and furthermore, a new allele (isoleucine, Ile) emerged and increased its frequencies around the world.

Previous reports suggested that people with the Ile genotype were less prone to depression and anxiety than those with the Thr genotype, but it was unclear how these human-specific mutations work in the brain and lead to changes in neuropsychiatric behavior.

In this study, Sato, Kawata (Tohoku University), Yukiko U. Inoue (National Center for Neurology and Psychiatry), and colleagues prepared Vmat1 gene-modified mice in which the 136th amino acid locus was replaced by human genotype (Thr or Ile) via genome editing technology, and compared gene expression, neuronal activity and behavior between genotypes.

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The functional role of the VMAT1 gene in the central nervous system remains unclear, and this study may provide a stepping stone towards elucidating its molecular mechanisms. Image is in public domain

Ile-type mice showed decreased levels of anxious behaviors, consistent with human studies. Additionally, genotype affected post-synaptic gene expression and neuronal activity in the amygdala, a brain region involved in emotional regulation.

The functional role of the VMAT1 gene in the central nervous system remains unclear, and this study may provide a stepping stone towards elucidating its molecular mechanisms.

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Additionally, there are few studies in which the effects of single amino acid substitutions under natural selection during human evolution have been verified using genome editing technology.

This study demonstrates the functional importance of human-specific variants in neurotransmitter regulatory circuits involved in cognitive and emotional functions and should shed light on the pathogenic mechanisms of neuropsychiatric disorders such as anxiety and depression.

About this genetics, evolution and psychology research news

Author: Press office
Source: Tohoku University
Contact: Press Office – Tohoku University
Image: Image is in public domain

Original research: Free access.
“Humanized Vmat1 substitutions in mice alter amygdala-dependent behaviors associated with the course of anxiety” by Daiki X. Sato et al. iScience

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