Türkdönmez Ak Elif, Okuyucu Büşra, Arslan Gökhan, Ağar Erdal, Ayyildiz Mustafa
Department of Physiology, Faculty of Medicine, University of Ordu, Ordu, Türkiye.
Department of Physiology, Faculty of Medicine, University of Ondokuz Mayıs, Samsun, Türkiye.
Neurochem Res. 2025 Jan 3;50(1):67. doi: 10.1007/s11064-024-04318-2.
In the present study, the effects of the acetylcholinesterase (AChE) enzyme inhibitor rivastigmine (RIVA) on spike-wave discharges (SWDs), memory impairment, anxiety-like behavior, and the transient receptor potential vanilloid 1 (TRPV1) gene expression were investigated in genetic absence epileptic Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. After tripolar electrodes were implanted on the WAG/Rij rats' skulls, single doses of 0.125, 0.25, 0.5, 1, and 2 mg/kg RIVA were intraperitoneally (i.p.) administered, and electrocorticogram (ECoG) recordings of SWDs were recorded for three hours before and after injections. Additionally, once significant doses were determined in acute studies, WAG/Rij rats were administered low-dose (0.5 mg/kg) and high-dose (2 mg/kg) of RIVA for 21 consecutive days and SWDs were recorded. Learning-memory abilities (Y-maze test), anxiety-like behavior (elevated plus maze test), and TRPV1 gene expression were determined and compared in 8-month-old WAG/Rij and age-matched Wistar rats. Acute RIVA administration dose-dependently reduced the total number of SWDs and was even entirely inhibited at 1 and 2 mg/kg RIVA doses. On the other hand, long-term high-dose RIVA administration increased the total number of SWDs. Long-term high-dose RIVA treatment reduced learning-memory and anxiety-like behavior in WAG/Rij rats, while only anxiety-like behavior decreased in Wistar rats. TRPV1 gene expression increased in WAG/Rij rats and decreased in Wistar rats with long-term RIVA administration. These data indicate that the sudden increase of acetylcholine (ACh) causes a significant decrease in absence seizures. In contrast, prolonged maintenance of ACh elevation causes an increase in absence seizures, probably by altering the expression of channels such as TRPV1.
在本研究中，在遗传性失神癫痫Wistar白化Glaxo/Rijswijk（WAG/Rij）大鼠中研究了乙酰胆碱酯酶（AChE）抑制剂卡巴拉汀（RIVA）对棘波放电（SWDs）、记忆障碍、焦虑样行为和瞬时受体电位香草酸亚型1（TRPV1）基因表达的影响。在WAG/Rij大鼠颅骨上植入三极电极后，腹腔内（i.p.）给予单剂量0.125、0.25、0.5、1和2mg/kg的RIVA，并在注射前后3小时记录SWDs的脑电图（ECoG）。此外，在急性研究确定有效剂量后，连续21天给WAG/Rij大鼠低剂量（0.5mg/kg）和高剂量（2mg/kg）的RIVA，并记录SWDs。在8月龄的WAG/Rij大鼠和年龄匹配的Wistar大鼠中测定并比较学习记忆能力（Y迷宫试验）、焦虑样行为（高架十字迷宫试验）和TRPV1基因表达。急性给予RIVA剂量依赖性地减少了SWDs的总数，在1和2mg/kg RIVA剂量时甚至完全被抑制。另一方面，长期高剂量给予RIVA增加了SWDs的总数。长期高剂量RIVA治疗降低了WAG/Rij大鼠的学习记忆和焦虑样行为，而Wistar大鼠仅焦虑样行为减少。长期给予RIVA后，WAG/Rij大鼠的TRPV1基因表达增加，Wistar大鼠的TRPV1基因表达减少。这些数据表明，乙酰胆碱（ACh）的突然增加会导致失神发作显著减少。相反，ACh升高的长期维持可能通过改变TRPV1等通道的表达导致失神发作增加。
