Psychedelics Promote Structural and Functional Neural Plasticity.
Psychedelics Promote Structural and Functional Neural Plasticity.
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DOI：
10.1016/j.celrep.2018.05.022
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发表时间：
2018-06-12
期刊：
影响因子：
8.8
通讯作者：
Olson DE
中科院分区：
文献类型：
--
作者：
Ly C;Greb AC;Cameron LP;Wong JM;Barragan EV;Wilson PC;Burbach KF;Soltanzadeh Zarandi S;Sood A;Paddy MR;Duim WC;Dennis MY;McAllister AK;Ori-McKenney KM;Gray JA;Olson DE
前额叶皮质(PFC)神经元萎缩在抑郁症及相关疾病的病理生理学中起关键作用。据推测，促进前额叶细胞结构和功能可塑性的能力是解离麻醉剂氯胺酮快速作用的抗抑郁特性的基础。在这里，我们报告，与氯胺酮一样，5-羟色胺能迷幻剂在体外和体内都能够强劲地促进神经发生和/或脊髓形成。根据荧光显微镜和电生理学的测量，神经元结构的这些变化伴随着突触数量和功能的增加。迷幻剂引起的结构变化似乎是由于TrkB、mTOR和5-HT2A信号通路的刺激导致的，可能解释了这些化合物的临床疗效。我们的结果强调了迷幻剂的治疗潜力，重要的是，确定了几种用于药物化学努力的铅支架，这些支架专注于开发促进可塑性的化合物，作为治疗抑郁症和相关疾病的安全、有效和快速的治疗方法。Ly等人。证明迷幻化合物，如LSD，DMT和DOI，增加了树突棘的复杂性，促进了树突棘的生长，并刺激了突触的形成。这些细胞效应类似于快速作用的抗抑郁剂氯胺酮产生的效应，并突显了迷幻剂治疗抑郁症和相关疾病的潜力。
Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders. Ly et al. demonstrate that psychedelic compounds such as LSD, DMT, and DOI increase dendritic arbor complexity, promote dendritic spine growth, and stimulate synapse formation. These cellular effects are similar to those produced by the fast-acting antidepressant ketamine and highlight the potential of psychedelics for treating depression and related disorders.
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影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
影响因子：
34.7
作者：
Arnsten, Amy F. T.
通讯作者：
Arnsten, Amy F. T.
影响因子：
3.7
作者：
Castello NA;Nguyen MH;Tran JD;Cheng D;Green KN;LaFerla FM
通讯作者：
LaFerla FM
影响因子：
3.6
作者：
Appel, JB;West, WB;Pechersky, K
通讯作者：
Pechersky, K
DOI：
10.4088/jcp.09m05327blu
发表时间：
2010-12
期刊：
The Journal of clinical psychiatry
影响因子：
--
作者：
DiazGranados N;Ibrahim LA;Brutsche NE;Ameli R;Henter ID;Luckenbaugh DA;Machado-Vieira R;Zarate CA Jr
通讯作者：
Zarate CA Jr