Neuroglialpharmacology: myelination as a shared mechanism of action of psychotropic treatments.
Neuroglialpharmacology: myelination as a shared mechanism of action of psychotropic treatments.
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DOI：
10.1016/j.neuropharm.2012.01.015
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发表时间：
2012-06
影响因子：
4.7
通讯作者：
Bartzokis G
中科院分区：
文献类型：
--
作者：
Bartzokis G
目前的精神病学诊断方案将症状群分成离散的实体，然而，很大一部分患者患有既不适合诊断也不适合治疗方案的共病。同样，从锂盐和抗精神病药物到血清素再摄取抑制剂 (SSRI) 和乙酰胆碱酯酶抑制剂等精神治疗药物已被证明对多种精神疾病有效，包括自闭症、精神分裂症 (SZ)、抑郁症、双相情感障碍 (BD) 和阿尔茨海默病 (AD)。这种明显缺乏特异性表明，精神症状和治疗可能具有共同的病理生理学和作用机制，违背了当前基于症状的诊断和基于神经元的治疗方案。以髓磷脂为中心的人脑功能模型可以帮助整合这些不协调之处，并为疾病病因和治疗机制提供新的见解。本文整合的现有数据表明，广泛使用的精神治疗药物（从抗精神病药和抗抑郁药到锂剂和电惊厥疗法）共享复杂的信号传导途径，例如影响髓鞘形成、其可塑性和修复的 Akt 和糖原合酶激酶 3 (GSK3)。这些信号通路对神经递质、神经营养蛋白、激素和营养作出反应，是复杂的神经胶质细胞通讯的基础，并且可能通过促进髓鞘形成，对当前治疗方法的作用机制和广泛功效做出重大贡献。成像和遗传技术使得直接在人体中安全、无创地测试这些假设成为可能，并有助于指导旨在纠正髓鞘形成异常的临床试验工作。这些努力可能会为治疗和预防一些最流行和最具破坏性的人类疾病提供新的途径。普遍的大脑髓鞘形成是神经网络同步和我们作为一个物种的独特性的基础。精神病学诊断可能存在髓磷脂发育、可塑性或修复方面的缺陷。治疗作用于神经胶质信号通路，例如 Akt 和 GSK3，可改善髓鞘形成。治疗效果可能源自髓鞘形成驱动的神经网络同步的改善。 “神经胶质药理学”概括了药物开发策略的范式转变。
Current psychiatric diagnostic schema segregate symptom clusters into discrete entities, however, large proportions of patients suffer from comorbid conditions that fit neither diagnostic nor therapeutic schema. Similarly, psychotropic treatments ranging from lithium and antipsychotics to serotonin reuptake inhibitors (SSRIs) and acetylcholinesterase inhibitors have been shown to be efficacious in a wide spectrum of psychiatric disorders ranging from autism, schizophrenia (SZ), depression, and bipolar disorder (BD) to Alzheimer’s disease (AD). This apparent lack of specificity suggests that psychiatric symptoms as well as treatments may share aspects of pathophysiology and mechanisms of action that defy current symptom-based diagnostic and neuron-based therapeutic schema. A myelin-centered model of human brain function can help integrate these incongruities and provide novel insights into disease etiologies and treatment mechanisms. Available data are integrated herein to suggest that widely used psychotropic treatments ranging from antipsychotics and antidepressants to lithium and electroconvulsive therapy share complex signaling pathways such as Akt and glycogen synthase kinase-3 (GSK3) that affect myelination, its plasticity, and repair. These signaling pathways respond to neurotransmitters, neurotrophins, hormones, and nutrition, underlie intricate neuroglial communications, and may substantially contribute to the mechanisms of action and wide spectra of efficacy of current therapeutics by promoting myelination. Imaging and genetic technologies make it possible to safely and noninvasively test these hypotheses directly in humans and can help guide clinical trial efforts designed to correct myelination abnormalities. Such efforts may provide insights into novel avenues for treatment and prevention of some of the most prevalent and devastating human diseases. Pervasive brain myelination underlies neural network synchrony and our distinctiveness as a species. Psychiatric diagnoses may share deficits in myelin development, plasticity, or repair. Treatments act on neuroglial signaling pathways such as Akt and GSK3 that improve myelination. Treatment efficacy may derive from myelination-driven improved neural network synchronization. “Neuroglialpharmacology” encapsulates a paradigm shift in medication development strategy.
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影响因子：
3.7
作者：
Astarita G;Jung KM;Berchtold NC;Nguyen VQ;Gillen DL;Head E;Cotman CW;Piomelli D
通讯作者：
Piomelli D
影响因子：
11
作者：
Anacker, C.;Zunszain, P. A.;Cattaneo, A.;Carvalho, L. A.;Garabedian, M. J.;Thuret, S.;Price, J.;Pariante, C. M.
通讯作者：
Pariante, C. M.
影响因子：
3.5
作者：
Balu, Darrick T.;Carlson, Gregory C.;Talbot, Konrad;Kazi, Hala;Hill-Smith, Tiffany E.;Easton, Rachel M.;Birnbaum, Morris J.;Lucki, Irwin
通讯作者：
Lucki, Irwin
影响因子：
--
作者：
Amminger, G. Paul;Schafer, Miriam R.;Berger, Gregor E.
通讯作者：
Berger, Gregor E.
影响因子：
--
作者：
Bartzokis, G;Beckson, M;Mintz, J
通讯作者：
Mintz, J