Departamento de Ciências Fisiológicas, Universidade do Estado do Rio de Janeiro, Brazil.
Pharmacol Biochem Behav. 2013 Jan;103(3):684-91. doi: 10.1016/j.pbb.2012.11.007. Epub 2012 Nov 21.
The brain is extremely vulnerable to teratogenic insults during the brain growth spurt, a period that starts during the third trimester of human gestation and is characterized by synaptogenesis establishment of neuronal circuits. While the treatment of epilepsy during pregnancy increases the risk of neurodevelopmental disorders in offspring, the consequences of exposure to anticonvulsants during the brain growth spurt remain poorly known. Here we investigate whether exposure to sodium valproate (VPA) during a similar period in rats impairs spatial learning of juvenile rats. Long-Evans rats were exposed to VPA (200mg/kg) or saline solution (SAL) every other day between postnatal day (PN) 4 and PN10. At PN23 and PN30, Morris water maze performance was evaluated during 6 consecutive days. In the group of animals which started their tests at PN23, the VPA exposure impaired both, swimming speed and learning/memory performance. Interestingly, no differences were observed between VPA and control animals tested from PN30 to PN35. Our data suggests that the neurobehavioral deficits caused by VPA exposure during the brain growth spurt are transitory.
大脑在脑生长突增期极易受到致畸因素的影响,这一时期始于人类妊娠的第三个三个月,其特征是突触形成神经元回路的建立。虽然怀孕期间治疗癫痫会增加后代神经发育障碍的风险,但在脑生长突增期接触抗惊厥药物的后果知之甚少。在这里,我们研究了在类似的大鼠发育期给予丙戊酸钠(VPA)是否会损害幼年大鼠的空间学习能力。长耳大鼠在出生后第 4 天至第 10 天每隔一天接受 VPA(200mg/kg)或生理盐水(SAL)处理。在 PN23 和 PN30 时,在连续 6 天内评估 Morris 水迷宫性能。在从 PN23 开始测试的动物组中,VPA 暴露既损害了游泳速度,也损害了学习/记忆表现。有趣的是,从 PN30 到 PN35 测试的 VPA 和对照动物之间没有观察到差异。我们的数据表明,VPA 暴露在脑生长突增期引起的神经行为缺陷是暂时的。