Watanabe Hiroyuki, Fitting Sylvia, Hussain Muhammad Z, Kononenko Olga, Iatsyshyna Anna, Yoshitake Takashi, Kehr Jan, Alkass Kanar, Druid Henrik, Wadensten Henrik, Andren Per E, Nylander Ingrid, Wedell Douglas H, Krishtal Oleg, Hauser Kurt F, Nyberg Fred, Karpyak Victor M, Yakovleva Tatjana, Bakalkin Georgy
Division of Biological Research on Drug Dependence, Department of Pharmaceutical Biosciences.
Department of Pharmacology and Toxicology.
Cereb Cortex. 2015 Jan;25(1):97-108. doi: 10.1093/cercor/bht204. Epub 2013 Aug 19.
Lateralization of the processing of positive and negative emotions and pain suggests an asymmetric distribution of the neurotransmitter systems regulating these functions between the left and right brain hemispheres. By virtue of their ability to selectively mediate euphoria, dysphoria, and pain, the μ-, δ-, and κ-opioid receptors and their endogenous ligands may subserve these lateralized functions. We addressed this hypothesis by comparing the levels of the opioid receptors and peptides in the left and right anterior cingulate cortex (ACC), a key area for emotion and pain processing. Opioid mRNAs and peptides and 5 "classical" neurotransmitters were analyzed in postmortem tissues from 20 human subjects. Leu-enkephalin-Arg (LER) and Met-enkephalin-Arg-Phe, preferential δ-/μ- and κ-/μ-opioid agonists, demonstrated marked lateralization to the left and right ACC, respectively. Dynorphin B (Dyn B) strongly correlated with LER in the left, but not in the right ACC suggesting different mechanisms of the conversion of this κ-opioid agonist to δ-/μ-opioid ligand in the 2 hemispheres; in the right ACC, Dyn B may be cleaved by PACE4, a proprotein convertase regulating left-right asymmetry formation. These findings suggest that region-specific lateralization of neuronal networks expressing opioid peptides underlies in part lateralization of higher functions, including positive and negative emotions and pain in the human brain.
积极与消极情绪及疼痛处理过程的偏侧化表明，调节这些功能的神经递质系统在左右脑半球之间呈不对称分布。凭借其选择性介导欣快感、烦躁不安及疼痛的能力，μ-、δ-和κ-阿片受体及其内源性配体可能有助于这些偏侧化功能。我们通过比较左右前扣带回皮质（ACC，情绪和疼痛处理的关键区域）中阿片受体和肽的水平来验证这一假设。对20名人类受试者的死后组织中的阿片mRNA、肽以及5种“经典”神经递质进行了分析。亮氨酸脑啡肽-精氨酸（LER）和甲硫氨酸脑啡肽-精氨酸-苯丙氨酸，分别为优先的δ-/μ-和κ-/μ-阿片激动剂，在左右ACC中表现出明显的偏侧化。强啡肽B（Dyn B）在左侧ACC中与LER强烈相关，而在右侧ACC中则不然，这表明在两个半球中这种κ-阿片激动剂转化为δ-/μ-阿片配体的机制不同；在右侧ACC中，Dyn B可能被PACE4切割，PACE4是一种调节左右不对称形成的前体蛋白转化酶。这些发现表明，表达阿片肽的神经网络的区域特异性偏侧化部分地构成了包括人类大脑中的积极和消极情绪及疼痛在内的高级功能偏侧化的基础。
