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阿尔茨海默病Tg4-42模型中听觉惊吓反应和前脉冲抑制的降低

Reduced Acoustic Startle Response and Prepulse Inhibition in the Tg4-42 Model of Alzheimer's Disease.

作者信息

Sichler Marius E, Löw Maximilian J, Schleicher Eva M, Bayer Thomas A, Bouter Yvonne

机构信息

Division of Molecular Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center Goettingen (UMG), Georg-August-University, Goettingen, Germany.

出版信息

J Alzheimers Dis Rep. 2019 Nov 21;3(1):269-278. doi: 10.3233/ADR-190132.

Abstract

Sensorimotor deficits have been described in several neuropsychiatric disorders including Alzheimer's disease. The aim of the present study was to evaluate possible sensorimotor gating deficits in the Tg4-42 mouse model of Alzheimer's disease using the prepulse inhibition task (PPI). Previous studies indicated that the hippocampus is essentially involved in the regulation of PPI. We analyzed 7-month-old homozygous Tg4-42 mice as mice at this age display severe neuron loss especially in the CA1 region of the hippocampus. Our results revealed a reduced startle response and PPI in Tg4-42 mice. The observed deficits in startle response and PPI are likely due to altered sensory processing abilities rather than hearing deficits as Tg4-42 displayed intact hearing in the fear conditioning task. The present study demonstrates for the first time that sensorimotor gating is impaired in Tg4-42 mice. Analyzing startle response as well as the PPI may offer valuable measurements to assess the efficacy of therapeutic strategies in the future in this Alzheimer's disease model.

摘要

感觉运动缺陷已在包括阿尔茨海默病在内的多种神经精神疾病中有所描述。本研究的目的是使用预脉冲抑制任务(PPI)评估阿尔茨海默病Tg4-42小鼠模型中可能存在的感觉运动门控缺陷。先前的研究表明,海马体在PPI的调节中起重要作用。我们分析了7个月大的纯合Tg4-42小鼠,因为这个年龄段的小鼠表现出严重的神经元丧失,尤其是在海马体的CA1区域。我们的结果显示,Tg4-42小鼠的惊吓反应和PPI降低。观察到的惊吓反应和PPI缺陷可能是由于感觉处理能力改变,而非听力缺陷,因为Tg4-42在恐惧条件反射任务中表现出正常听力。本研究首次证明Tg4-42小鼠存在感觉运动门控受损。分析惊吓反应以及PPI可能为评估未来该阿尔茨海默病模型中治疗策略的疗效提供有价值的测量方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b483/6918877/f4ffedd70a13/adr-3-adr190132-g001.jpg

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