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胆碱胞嘧啶核苷和加兰他敏,一种针对α7 烟碱型乙酰胆碱受体的个体化靶向治疗,用于调节健康志愿者语音 MMN 索引偏差检测:一项初步研究。

CDP-choline and galantamine, a personalized α7 nicotinic acetylcholine receptor targeted treatment for the modulation of speech MMN indexed deviance detection in healthy volunteers: a pilot study.

机构信息

Department of Neuroscience, Faculty of Medicine, University of Ottawa, 1145 Carling Ave, Ottawa, ON, K1Z 7K4, Canada.

Department of Psychiatry, The Royal Ottawa Mental Health Centre, Ottawa, ON, Canada.

出版信息

Psychopharmacology (Berl). 2020 Dec;237(12):3665-3687. doi: 10.1007/s00213-020-05646-1. Epub 2020 Aug 27.

Abstract

RATIONALE

The combination of CDP-choline, an α7 nicotinic acetylcholine receptor (α7 nAChR) agonist, with galantamine, a positive allosteric modulator of nAChRs, is believed to counter the fast desensitization rate of the α7 nAChRs and may be of interest for schizophrenia (SCZ) patients. Beyond the positive and negative clinical symptoms, deficits in early auditory prediction-error processes are also observed in SCZ. Regularity violations activate these mechanisms that are indexed by electroencephalography-derived mismatch negativity (MMN) event-related potentials (ERPs) in response to auditory deviance.

OBJECTIVES/METHODS: This pilot study in thirty-three healthy humans assessed the effects of an optimized α7 nAChR strategy combining CDP-choline (500 mg) with galantamine (16 mg) on speech-elicited MMN amplitude and latency measures. The randomized, double-blinded, placebo-controlled, and counterbalanced design with a baseline stratification method allowed for assessment of individual response differences.

RESULTS

Increases in MMN generation mediated by the acute CDP-choline/galantamine treatment in individuals with low baseline MMN amplitude for frequency, intensity, duration, and vowel deviants were revealed.

CONCLUSIONS

These results, observed primarily at temporal recording sites overlying the auditory cortex, implicate α7 nAChRs in the enhancement of speech deviance detection and warrant further examination with respect to dysfunctional auditory deviance processing in individuals with SCZ.

摘要

原理

CDP-胆碱,一种α7 烟碱型乙酰胆碱受体(α7 nAChR)激动剂,与加兰他敏(nAChRs 的正变构调节剂)联合使用,被认为可以抵消α7 nAChR 的快速脱敏速率,并且可能对精神分裂症(SCZ)患者有兴趣。除了阳性和阴性的临床症状外,在 SCZ 中还观察到早期听觉预测误差过程中的缺陷。规律性违反激活了这些机制,这些机制通过脑电图衍生的失匹配负波(MMN)事件相关电位(ERPs)在听觉偏差时被索引。

目的/方法:这项在 33 名健康人类中的初步研究评估了优化的α7 nAChR 策略联合 CDP-胆碱(500mg)和加兰他敏(16mg)对言语诱发的 MMN 幅度和潜伏期测量的影响。随机、双盲、安慰剂对照和平衡设计与基线分层方法允许评估个体反应差异。

结果

在个体的基线 MMN 幅度较低的情况下,急性 CDP-胆碱/加兰他敏治疗增加了频率、强度、持续时间和元音偏差的 MMN 产生,揭示了这种增加。

结论

这些结果主要在听觉皮层上方的时间记录部位观察到,表明α7 nAChR 参与了增强言语偏差检测,并需要进一步研究 SCZ 个体中功能失调的听觉偏差处理。

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