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失神癫痫基因大鼠模型中的行为和认知共病(聚焦于GAERS和WAG/Rij大鼠)

Behavioral and Cognitive Comorbidities in Genetic Rat Models of Absence Epilepsy (Focusing on GAERS and WAG/Rij Rats).

作者信息

Sitnikova Evgenia

机构信息

Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 5A Butlerova St., Moscow 117485, Russia.

出版信息

Biomedicines. 2024 Jan 7;12(1):122. doi: 10.3390/biomedicines12010122.

Abstract

Absence epilepsy is a non-convulsive type of epilepsy characterized by the sudden loss of awareness. It is associated with thalamo-cortical impairment, which may cause neuropsychiatric and neurocognitive problems. Rats with spontaneous absence-like seizures are widely used as in vivo genetic models for absence epilepsy; they display behavioral and cognitive problems similar to epilepsy in humans, such as genetic absence epilepsy rats from Strasbourg (GAERS) and Wistar Albino rats from Rijswijk (WAG/Rij). Depression- and anxiety-like behaviors were apparent in GAERS, but no anxiety and depression-like symptoms were found in WAG/Rij rats. Deficits in executive functions and memory impairment in WAG/Rij rats, i.e., cognitive comorbidities, were linked to the severity of epilepsy. Wistar rats can develop spontaneous seizures in adulthood, so caution is advised when using them as a control epileptic strain. This review discusses challenges in the field, such as putative high emotionality in genetically prone rats, sex differences in the expression of cognitive comorbidities, and predictors of cognitive problems or biomarkers of cognitive comorbidities in absence epilepsy, as well as the concept of "the cognitive thalamus". The current knowledge of behavioral and cognitive comorbidities in drug-naive rats with spontaneous absence epilepsy is beneficial for understanding the pathophysiology of absence epilepsy, and for finding new treatment strategies.

摘要

失神癫痫是一种非惊厥性癫痫,其特征为突然意识丧失。它与丘脑 - 皮质损伤有关,这可能会导致神经精神和神经认知问题。具有自发性失神样发作的大鼠被广泛用作失神癫痫的体内遗传模型;它们表现出与人类癫痫相似的行为和认知问题,例如来自斯特拉斯堡的遗传性失神癫痫大鼠(GAERS)和来自赖斯韦克的Wistar白化大鼠(WAG/Rij)。GAERS中出现了抑郁样和焦虑样行为,但在WAG/Rij大鼠中未发现焦虑和抑郁样症状。WAG/Rij大鼠的执行功能缺陷和记忆障碍,即认知共病,与癫痫的严重程度有关。Wistar大鼠在成年后会出现自发性癫痫发作,因此在将它们用作对照癫痫品系时需谨慎。本综述讨论了该领域的挑战,如遗传易患大鼠中假定的高情绪性、认知共病表达中的性别差异、失神癫痫中认知问题的预测因素或认知共病的生物标志物,以及“认知丘脑”的概念。目前对未经药物治疗的自发性失神癫痫大鼠行为和认知共病的了解,有助于理解失神癫痫的病理生理学,并找到新的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32da/10812980/3469a36824a3/biomedicines-12-00122-g001.jpg

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