Transient Stimulation with Psychoplastogens Is Sufficient to Initiate Neuronal Growth,ACS Pharmacology & Translational Science

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Transient Stimulation with Psychoplastogens Is Sufficient to Initiate Neuronal Growth
ACS Pharmacology & Translational Science ( IF 4.9 ) Pub Date : 2020-09-11 , DOI: 10.1021/acsptsci.0c00065
Calvin Ly ₁ , Alexandra C Greb ₁ , Maxemiliano V Vargas ₂ , Whitney C Duim ₁ , Ana Cristina G Grodzki ₃ , Pamela J Lein ₃ , David E Olson _{1,

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Affiliation

Cortical neuron atrophy is a hallmark of depression and includes neurite retraction, dendritic spine loss, and decreased synaptic density. Psychoplastogens, small molecules capable of rapidly promoting cortical neuron growth, have been hypothesized to produce long-lasting positive effects on behavior by rectifying these deleterious structural and functional changes. Here we demonstrate that ketamine and LSD, psychoplastogens from two structurally distinct chemical classes, promote sustained growth of cortical neurons after only short periods of stimulation. Furthermore, we show that psychoplastogen-induced cortical neuron growth can be divided into two distinct epochs: an initial stimulation phase requiring TrkB activation and a growth period involving sustained mTOR and AMPA receptor activation. Our results provide important temporal details concerning the molecular mechanisms by which next-generation antidepressants produce persistent changes in cortical neuron structure, and they suggest that rapidly excreted psychoplastogens might still be effective neurotherapeutics with unique advantages over compounds like ketamine and LSD.

中文翻译：

精神塑性原的瞬时刺激足以启动神经元生长

皮质神经元萎缩是抑郁症的标志，包括神经突回缩、树突棘丢失和突触密度降低。精神塑性原是一种能够快速促进皮层神经元生长的小分子，已被假设通过纠正这些有害的结构和功能变化对行为产生持久的积极影响。在这里，我们证明氯胺酮和 LSD，来自两种结构不同的化学类别的精神塑性原，仅在短时间刺激后促进皮层神经元的持续生长。此外，我们表明，psychoplastogen 诱导的皮层神经元生长可分为两个不同的时期：需要 TrkB 激活的初始刺激阶段和涉及持续 mTOR 和 AMPA 受体激活的生长期。

更新日期：2020-09-11

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