GABA-Transaminase antisense oligodeoxynucleotide modulates cocaine- and pentylenetetrazol-induced seizures in mice
GABA-Transaminase antisense oligodeoxynucleotide modulates cocaine- and pentylenetetrazol-induced seizures in mice
复制标题
DOI：
10.1023/a:1020737125843
复制
发表时间：
1999-12-01
影响因子：
3.6
通讯作者：
Kohli, N
中科院分区：
文献类型：
--
作者：
Abel, MS;Kohli, N
许多抗惊厥药物的作用机制是增强GABA能系统的功能。抑制GABA-转氨酶(GABA-T)是GABA的降解酶，会增加大脑中的GABA水平。在本研究中，针对GABA-转氨酶mRNA起始密码子区域的反义寡核苷酸(ASO)被用来修饰癫痫的活性。小鼠接受脑室注射，给予反义寡核苷酸或适当对照。在治疗后的不同时间，用可卡因(70 mg/kg)激发动物。并观察癫痫发作活动。治疗15h后，1.152和1.44nmoL反义寡核苷酸阻断可卡因诱导的癫痫发作。反义寡核苷酸治疗后8h和36h均无作用。此外，7.2nmol反义寡核苷酸治疗可预防戊四氮诱发的癫痫发作。这些数据表明反义寡核苷酸对GABA-T的致痫阈值有调节作用。
The mechanism of action of many anticonvulsive agents is to increase the function of the GABAergic system. Inhibition of GABA-Transaminase (GABA-T), the degradative enzyme for GABA, increases GABA levels in the brain. In this study, antisense oligodeoxynucleotides (ASO) targeted at the start codon region of GABA-Transaminase mRNA were used to modify seizure activity. Mice were treated, by intracerebroventricular injection, with antisense oligos or appropriate controls. At various times after treatment, the animals were challenged with cocaine (70 mg/kg, i.p.) and observed for seizure activity. At 15 hours after treatment, 1.152 and 1.44 nmol antisense oligo blocked cocaine-induced seizures. There was no effect of antisense oligo 8 or 36 hours after treatment. In addition, treatment with 7.2 nmol antisense oligo prevented pentylenetetrazol-induced seizures. These data demonstrate the modulation of seizure threshold using antisense oligodeoxynucleotides to GABA-T.