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与感染和微生物组改变相关的儿科神经精神综合征:临床发现、黏膜上皮的可能作用,以及新动物模型的开发策略。

Pediatric neuropsychiatric syndromes associated with infection and microbiome alterations: clinical findings, possible role of the mucosal epithelium, and strategies for the development of new animal models.

机构信息

Centro de Investigación en Reproducción Animal Dr. Carlos Beyer Flores (CIRA), Universidad Autónoma de Tlaxcala - Centro de Investigación de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Tlaxcala, Mexico.

出版信息

Expert Opin Drug Discov. 2022 Jul;17(7):717-731. doi: 10.1080/17460441.2022.2074396. Epub 2022 May 30.

Abstract

INTRODUCTION

Pediatric obsessive-compulsive disorder (OCD) and autism spectrum disorder (ASD) have been associated with respiratory tract infections and alterations in the intestinal microbiome, respectively. Pediatric Acute-onset Neuropsychiatric Syndromes (PANS) refers to the sudden onset of neuropsychiatric symptoms that are triggered by several infectious and non-infectious factors. Studies indicate that inflammation plays an important etiological role in PANS, as well as in ASD associated with gut dysbiosis.

AREAS COVERED

The present review provides an overview of clinical studies of PANS and ASD associated with gastrointestinal symptoms, as well as existing strategies for investigating these syndromes in rodent models. The authors highlight similarities between these syndromes that may provide clues to common etiological mechanisms.

EXPERT OPINION

Although data from animal models are consistent with an important role for anti-neuronal antibodies in PANS triggered by GAS infection, we lack models for identifying pathophysiological mechanisms of PANS associated with other infectious and noninfectious triggers. The authors propose an animal modeling strategy that incorporates known vulnerability and triggering factors for PANS into the modeling process. This novel strategy should expand our understanding of the pathophysiology of PANS, as well as facilitate the development of new pharmacological treatments for PANS and related syndromes.

摘要

简介

儿科强迫症(OCD)和自闭症谱系障碍(ASD)分别与呼吸道感染和肠道微生物组改变有关。儿科急性发作神经精神综合征(PANS)是指由多种感染和非感染因素引起的突发性神经精神症状。研究表明,炎症在 PANS 以及与肠道菌群失调相关的 ASD 中起着重要的病因作用。

涵盖领域

本综述概述了与胃肠道症状相关的 PANS 和 ASD 的临床研究,以及在啮齿动物模型中研究这些综合征的现有策略。作者强调了这些综合征之间的相似之处,这些相似之处可能为共同的病因机制提供线索。

专家意见

尽管来自动物模型的数据表明,抗神经元抗体在 GAS 感染引发的 PANS 中起着重要作用,但我们缺乏用于识别与其他感染和非感染性触发因素相关的 PANS 病理生理机制的模型。作者提出了一种动物建模策略,即将 PANS 的已知易感性和触发因素纳入建模过程。这种新策略应能增进我们对 PANS 病理生理学的理解,并促进针对 PANS 和相关综合征的新药物治疗的发展。

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