Dysfunction of AMPA receptor GluA3 is associated with aggressive behavior in human
Dysfunction of AMPA receptor GluA3 is associated with aggressive behavior in human
复制标题
AMPA 受体 GluA3 功能障碍与人类攻击行为有关
DOI：
10.1038/s41380-022-01659-8
复制
发表时间：
2022-06-13
影响因子：
11
通讯作者：
Shi，Yun Stone
中科院分区：
文献类型：
--
作者：
Peng，Shi-Xiao;Pei，Jingwen;Shi，Yun Stone
Inappropriate aggression in humans hurts the society, families and individuals. The genetic basis for aggressive behavior, however, remains largely elusive. In this study, we identified two rare missense variants in X-linkedGRIA3from male patients who showed syndromes featuring aggressive outbursts. Both G630R and E787G mutations in AMPA receptor GluA3 completely lost their ion channel functions. Furthermore, a guanine-repeat single nucleotide polymorphism (SNP, rs3216834) located in the first intron of humanGRIA3gene was found to regulate GluA3 expression with longer guanine repeats (rs3216834-10G/-11G) suppressing transcription compared to the shorter ones (-7G/-8G/-9G). Importantly, the distribution of rs3216834-10G/-11G was elevated in a male violent criminal sample from Chinese Han population. Using GluA3 knockout mice, we showed that the excitatory neurotransmission and neuronal activity in the medial prefrontal cortex (mPFC) was impaired. Expressing GluA3 back into the mPFC alleviated the aggressive behavior of GluA3 knockout mice, suggesting that the defects in mPFC explained, at least partially, the neural mechanisms underlying the aggressive behavior. Therefore, our study provides compelling evidence that dysfunction of AMPA receptor GluA3 promotes aggressive behavior.
