Ilbay Gul, Dogan Zeynep Ikbal, Balıkcı Aymen, Erdogan Seyda, Karaoglan Kahilogulları Akfer
Department of Physiology, Faculty of Medicine, Kocaeli University, Kocaeli 41100, Turkey.
Department of Neurology, Faculty of Medicine, Ankara University, Ankara 06560, Turkey.
Brain Sci. 2022 Mar 8;12(3):361. doi: 10.3390/brainsci12030361.
The present study aims to investigate effect of early caffeine exposure on epileptogenesis and occurrence of absence seizures and comorbid depression in adulthood. For this purpose, Wistar Albino Glaxo from Rijswijk (WAG/Rij) rats were enrolled in a control and two experimental groups on the 7th day after the delivery. The rats in experimental groups received either 10 or 20 mg/kg caffeine subcutaneously while animals in control group had subcutaneous injections of 0.9% saline. The injections started at postnatal day 7 (PND7) and were continued each day for 5 days. At 6-7 months of age, electroencephalogram (EEG) recordings and behavioral recordings in the forced swimming test, sucrose consumption/preference test and locomotor activity test were carried out. At 6 months of age, 10 mg/kg and 20 mg/kg caffeine-treated WAG/Rij rats showed increased immobility latency and active swimming duration in forced swimming test when compared with the untreated controls. In addition, 20 mg/kg caffeine treatment decreased immobility time. In sucrose preference/consumption tests, WAG/Rij rats in 10 mg/kg caffeine group demonstrated higher sucrose consumption and preference compared to untreated controls. The rats treated with 20 mg/kg caffeine showed higher sucrose preference compared to control rats. The exploratory activity of rats in the 10 mg/kg caffeine-treated group was found to be higher than in the 20 mg/kg caffeine-treated and control groups in the locomotor activity test. At 7 months of age, caffeine-treated animals showed a decreased spike-wave discharge (SWD) number compared to the control animals. These results indicate that postnatal caffeine treatment may decrease the number of seizure and depression-like behaviors in WAG/Rij rats in later life. Caffeine blockade of adenosine receptors during the early developmental period may have beneficial effects in reducing seizure frequency and depression-like behaviors in WAG/Rij rat model.
本研究旨在探讨早期接触咖啡因对癫痫发生、失神发作的出现以及成年期共病抑郁的影响。为此,将来自荷兰里斯维克的Wistar白化病格拉克索(WAG/Rij)大鼠在分娩后第7天纳入一个对照组和两个实验组。实验组的大鼠皮下注射10或20mg/kg咖啡因,而对照组的动物皮下注射0.9%生理盐水。注射从出生后第7天(PND7)开始,每天持续进行5天。在6 - 7个月大时,进行脑电图(EEG)记录以及强迫游泳试验、蔗糖消耗/偏好试验和运动活动试验中的行为记录。在6个月大时,与未处理的对照组相比,10mg/kg和20mg/kg咖啡因处理的WAG/Rij大鼠在强迫游泳试验中静止潜伏期增加,主动游泳持续时间延长。此外,20mg/kg咖啡因处理减少了静止时间。在蔗糖偏好/消耗试验中,10mg/kg咖啡因组的WAG/Rij大鼠与未处理的对照组相比,表现出更高的蔗糖消耗和偏好。与对照大鼠相比,20mg/kg咖啡因处理的大鼠表现出更高的蔗糖偏好。在运动活动试验中,发现10mg/kg咖啡因处理组大鼠的探索活动高于20mg/kg咖啡因处理组和对照组。在7个月大时,与对照动物相比,咖啡因处理的动物棘波放电(SWD)次数减少。这些结果表明,出生后咖啡因处理可能会减少WAG/Rij大鼠成年后期的癫痫发作次数和抑郁样行为。在早期发育阶段咖啡因对腺苷受体的阻断可能对降低WAG/Rij大鼠模型的癫痫发作频率和抑郁样行为具有有益作用。
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