Neuroprotective effects of psilocybin in a rat model of stroke.

IF 2.4 4区医学 Q3 NEUROSCIENCES BMC Neuroscience Pub Date : 2024-10-08 DOI:10.1186/s12868-024-00903-x

Seong-Jin Yu, Kuo-Jen Wu, Yu-Syuan Wang, Eunkyung Bae, Fabio Chianelli, Nicholas Bambakidis, Yun Wang

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Abstract

Background: Psilocybin is a psychedelic 5HT2A receptor agonist found in "magic mushrooms". Recent studies have indicated that 5HT2A agonists, such as dimethyltryptamine, given before middle cerebral artery occlusion (MCAo), improve staircase behavior, increased BDNF expression, and reduce brain infarction in stroke rats. The objective of this study is to determine the protective effect of psilocybin in cellular and animal models of stroke.

Methods: Adult male and timed-pregnant Sprague-Dawley rats were used for this study. The neural protective effects of psilocybin were determined in primary rat cortical neurons and adult rats. Rats were subjected to a 60-min middle cerebral artery occlusion. Brain tissues were collected for histological and qRTPCR analysis.

Results: Psilocybin reduced glutamate-mediated neuronal loss in rat primary cortical neuronal cultures. Psilocybin-mediated protection in culture was antagonized by the BDNF inhibitor ANA12. Pretreatment with psilocybin reduced brain infarction and neurological deficits in stroke rats. Early post-treatment with psilocybin improved locomotor behavior, upregulated the expression of MAP2 and synaptophysin, and down-regulated the expression of IBA1 in the stroke brain. ANA12 significantly attenuated psilocybin-mediated reduction in brain infarction and improvements in locomotor behavior.

Conclusions: Psilocybin reduced brain infarction and improved locomotor behavior in stroke rats; the protective mechanisms involve regulating BDNF expression. Our data support a novel therapeutic approach of psilocybin in stroke.

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迷幻药对中风大鼠模型的神经保护作用。

背景介绍迷幻蘑菇中的迷幻药 5HT2A 受体激动剂。最近的研究表明，在大脑中动脉闭塞（MCAo）前给予 5HT2A 激动剂，如二甲基色胺，可改善中风大鼠的阶梯行为，增加 BDNF 的表达，减少脑梗塞。本研究的目的是确定迷幻药在中风细胞模型和动物模型中的保护作用：方法：本研究使用成年雄性大鼠和定时怀孕的 Sprague-Dawley 大鼠。方法：本研究使用成年雄性大鼠和定时怀孕的 Sprague-Dawley 大鼠，在原代大鼠皮质神经元和成年大鼠中测定迷幻药的神经保护作用。对大鼠进行 60 分钟的大脑中动脉闭塞。收集脑组织进行组织学和 qRTPCR 分析：结果：在大鼠原代皮层神经元培养物中，迷幻药减少了谷氨酸介导的神经元损失。BDNF 抑制剂 ANA12 可拮抗迷幻药介导的培养保护作用。用迷幻药预处理可减轻中风大鼠的脑梗塞和神经功能缺损。西洛滨治疗后早期可改善中风大鼠的运动行为，上调MAP2和突触素的表达，下调IBA1的表达。ANA12明显减弱了迷幻药介导的脑梗塞减少和运动行为改善：结论：迷幻药可减轻脑梗塞，改善中风大鼠的运动行为；其保护机制涉及调节 BDNF 的表达。我们的数据支持迷幻药治疗中风的新方法。

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来源期刊

BMC Neuroscience 医学-神经科学

CiteScore

3.90

自引率

0.00%

发文量

审稿时长

16 months

期刊介绍： BMC Neuroscience is an open access, peer-reviewed journal that considers articles on all aspects of neuroscience, welcoming studies that provide insight into the molecular, cellular, developmental, genetic and genomic, systems, network, cognitive and behavioral aspects of nervous system function in both health and disease. Both experimental and theoretical studies are within scope, as are studies that describe methodological approaches to monitoring or manipulating nervous system function.