Exendin-4 增加 WAG/Rij 大鼠的失神样发作和焦虑抑郁样行为。

Exendin-4 increases absence-like seizures and anxiety-depression-like behaviors in WAG/Rij rats.

机构信息

Department of Physiology, Faculty of Medicine, Tokat Gaziosmanpasa University, Tokat, Turkey.

出版信息

Epilepsy Behav. 2021 Oct;123:108246. doi: 10.1016/j.yebeh.2021.108246. Epub 2021 Aug 10.

Abstract

AIM

Epilepsy is a neurological condition affecting millions of people worldwide. Glucagon-like peptide-1 (GLP-1) is a gut hormone, and its neuroprotective effect was investigated in previous studies. In this study, the effects of exendin-4, a GLP-1 receptor agonist, were studied in genetic absence epileptic Wistar Albino Glaxo/Rijswijk rats (WAG/Rij). WAG/Rij rat is a genetic model of the absence epilepsy and depression-like comorbidity.

METHOD

We examined the effects of exendin-4 (10, 50 and 100 µg/kg) on the absence seizures (Electrocorticography [ECoG] recordings), anxiety level (open-field test [OF]), and depression-like levels (forced swimming test [FST]) in the WAG/Rij rats. Basal ECoG recording was performed for all rats. Then, exendin-4 (10, 50 or 100 µg/kg) was administered intraperitoneally and ECoG recording was made for 180 min. After ECoG recording, forced swimming test and open-field test were applied.

RESULTS

Administration of 10, 50, or 100 µg/kg exendin-4 increased the duration and number of spike-wave discharges (SWDs) considerably without changing the amplitude. The 100 µg/kg dose of exendin-4 was the most effective in increasing the total duration of SWDs. Additionally, all exendin-4 doses increased anxiety level in OF and depression-like level in FST.

CONCLUSION

Our results showed that exendin-4 increased SWD incidence and anxiety- and depression-like behaviors in the WAG/Rij rats. Besides, it was also found that high doses caused the most proabsence effect.

摘要

目的

癫痫是一种影响全球数百万人的神经系统疾病。胰高血糖素样肽-1(GLP-1)是一种肠道激素,其神经保护作用已在先前的研究中得到研究。在这项研究中,研究了 GLP-1 受体激动剂 exendin-4 在遗传缺失性癫痫 Wistar Albino Glaxo/Rijswijk 大鼠(WAG/Rij)中的作用。WAG/Rij 大鼠是一种癫痫和抑郁共病的遗传模型。

方法

我们研究了 exendin-4(10、50 和 100μg/kg)对 WAG/Rij 大鼠的癫痫发作(脑电图[ECoG]记录)、焦虑水平(旷场试验[OF])和抑郁样水平(强迫游泳试验[FST])的影响。所有大鼠均进行基础 ECoG 记录。然后,腹腔内给予 exendin-4(10、50 或 100μg/kg)并进行 180min 的 ECoG 记录。ECoG 记录后,进行强迫游泳试验和旷场试验。

结果

给予 10、50 或 100μg/kg exendin-4 可显著增加棘波放电(SWD)的持续时间和数量,而不改变振幅。100μg/kg 剂量的 exendin-4 最有效地增加了 SWD 的总持续时间。此外,所有 exendin-4 剂量均增加了 OF 中的焦虑水平和 FST 中的抑郁样水平。

结论

我们的结果表明,exendin-4 增加了 WAG/Rij 大鼠的 SWD 发生率以及焦虑和抑郁样行为。此外,还发现高剂量会引起最明显的致痫作用。

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