中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (3): 396-397.doi: 10.4103/1673-5374.179041

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

二甲基色胺:神经炎症和神经保护的生化“瑞士军刀”?

  

  • 收稿日期:2015-12-22 出版日期:2016-03-15 发布日期:2016-03-15

Dimethyltryptamine (DMT): a biochemical Swiss Army knife in neuroinflammation and neuroprotection?

Attila Szabo, Ede Frecska   

  1. Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary (Szabo A)
    Department of Psychiatry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary (Frecska E)
  • Received:2015-12-22 Online:2016-03-15 Published:2016-03-15
  • Contact: Attila Szabo, Ph.D., szattila@med.unideb.hu.

摘要:

炎症理论已成为现代医学中许多神经精神疾病的最新趋势。各种免疫机制主要是通过小胶质细胞活性而有助于疾病病因和症状的了解,如精神分裂症、双相型障碍、抑郁症或阿尔茨海默病。它们作为“守门人”通过受体识别模式(如Toll样受体或者RIG-I样受体)持续监测组织微环境中潜在的“危险信号”。二甲基色胺以及神经甾是孤独受体σ-1的内源性配体。二甲基色胺被证明内源存在于人脑以及身体的其他组织中,然而此类色胺的确切生理作用尚未得到确定。这种广谱激动剂可以作用在二甲基色胺调制的几个生理过程中,并通过孤独受体σ-1和5-羟色胺受体调节炎症。文章指出孤独受体σ-1激动剂的保护和神经再生作用已经在几种体外和体内研究中有过报道。选择性孤独受体σ-1激动剂2-(4- morpholinethyl)1苯基环己烷(PRE084)以及cutamesine已显示可以在多种病理条件中明显促进神经保护机制并显著增加神经元细胞的存活率和再生率,如创伤、自身免疫神经退行性疾病。个别的孤独受体σ-1刺激也已经被发现能够极大提高神经胶质细胞源性神经营养因子水平,并促进神经细胞的存活和分化。二甲基色胺通过孤独受体σ-1的神经再生潜力已经作为多种生化和生理机制存在,这便于将二甲基色胺和孤独受体σ-1运输结合到哺乳动物大脑。因此二甲基色胺作为天然的内源激动剂作用在孤独受体σ-1和5-羟色胺受体,这一假设为是一种独特的,具有多面药理本质,其在周围和脑组织中的免疫调节过程中起到许多重要的作用,并作为参与促进和诱导哺乳动物神经系统神经再生的关键因素。

Abstract:

The inflammatory theory of many neuropsychiatric illnesses has become an emerging trend in modern medicine. Various immune mechanisms – mainly via the activity of microglia – may contribute to the etiology and symptomatology of diseases, such as schizophrenia, bipolar disorder, depression, or Alzheimer’s disease. They act as ’gatekeepers’ continuously monitoring the tissue microenvironment for potential ’danger signals’ by means of their pattern recognition receptors, such as Toll-like receptors or RIG-I-like receptors. Tryptaminergic trace amines (e.g., N,N-dimethyltryptamine; DMT) as well as neurosteroids (e.g., dehydroepiandrosterone) are endogenous ligands of the Sig-1R. DMT was shown to be endogenously present in the human brain and in other tissues of the body, however the exact physiological role of this tryptamine has not been identified yet. This wide-spectrum agonist activity may allow DMT to modulate several physiological processes and regulate inflammation through the Sig-1R and 5-HTRs. Protective and neuroregenerative effects of Sig-1R agonists have been reported in several in vitro and in vivo studies. The selective Sig-1R agonists 2-(4-morpholinethyl)1 phenylcyclohexanecarboxylate (PRE084) and cutamesine have been shown to strongly promote neuroprotective mechanisms and significantly increase neuronal cell survival and regeneration under various conditions, such as traumas, autoimmunity, and neurodegenerative disorders. Specific Sig-1R stimulation has also been found to greatly increase the levels of the glial cell-derived neurotrophic factor (GDNF) that promotes neuronal cell survival and differentiation. The neuroregenerative potential of DMT through the Sig-1R has been suggested earlier as multiple biochemical and physiological mechanisms exist, which facilitate the transportation and binding of DMT to the Sig-1R in the mammalian brain. Thus DMT – as a natural, endogenous agonist atboth the Sig-1R and 5-HTRs – is hypothesized to be an unique, many-faced pharmacological entity, which has many important roles in the immunoregulatory processes of peripheral and brain tissues, as well as involved in the promotion and induction of neuroregeneration in the mammalian nervous system.