SNP rs10420324 in the AMPA receptor auxiliary subunit TARP γ-8 regulates the susceptibility to antisocial personality disorder.
Abstract
In the brain, AMPA receptors mediate fast excitatory neurotransmission, the dysfunction of which leads to neuropsychiatric disorders. Synaptic function of AMPA receptors is tightly controlled by a protein group called transmembrane AMPAR regulatory proteins (TARPs). TARP γ-8 (also known as CACNG8) preferentially expresses in the hippocampus, cortex and subcortical regions that are critical for emotion generation indicating its association with psychiatric disorders. Here, we identified rs10420324 (T/G), a SNP located in the human CACNG8 gene, regulated reporter gene expression in vitro and TARP γ-8 expression in the human brain. A guanine at the locus (rs10420324G) suppressed transcription likely through modulation of a local G-quadruplex DNA structure. Consistent with these observations, the frequency of rs10420324G was higher in patients with anti-social personality disorder (ASPD) than in controls, indicating that rs10420324G in CACNG8 is more voluntary for ASPD. We then characterized the behavior of TARP γ-8 knockout and heterozygous mice and found that consistent with ASPD patients who often exhibit impulsivity, aggression, risk taking, irresponsibility and callousness, a decreased γ-8 expression in mice displayed similar ...Continue Reading
References
Structural and Functional Architecture of AMPA-Type Glutamate Receptors and Their Auxiliary Proteins
Software Mentioned
Related Concepts
Related Feeds
Brain Circuits in Emotional Learning
The neuronal circuits within the cortico-limbic brain regions form networks that mediate emotional behavior. Areas specific to emotional learning include the basal amygdala and sublenticular extended amygdala region along with a supplemental motor area. Discover the latest research on brain circuits in emotional learning here.