Centro de Investigaciones Cerebrales, Universidad Veracruzana, Médicos y Odontólogos, s/n, Col. Unidad del Bosque, 91010 Xalapa, Veracruz, México.
Departamento de Farmacobiología, Cinvestav, Calzada de los Tenorios, 235, 14330 Col. Granjas Coapa, Ciudad de México, México.
An Acad Bras Cienc. 2021 Mar 15;93(2):e20190861. doi: 10.1590/0001-3765202120190861. eCollection 2021.
Autism spectrum disorder is associated with alterations in GABAergic and glutamatergic neurotransmission. Here, we aimed to determine the concentration of GABA, glutamate, glutamine, aspartate, taurine, and glycine in brain tissue and plasma of rats prenatally exposed to valproic acid (VPA), a well-characterized experimental model of autism. Pregnant rats were injected with VPA (600mg/Kg) during the twelfth-embryonic-day. Control rats were injected with saline. On the fourteen-postnatal-day, rats from both groups (males and females) were anesthetized, euthanized by decapitation and their brain dissected out. The frontal cortex, hippocampus, amygdala, brain stem and cerebellum were dissected and homogenized. Homogenates were centrifuged and supernatants were used to quantify amino acid concentrations by HPLC coupled with fluorometric detection. Blood samples were obtained by a cardiac puncture; plasma was separated and deproteinized to quantify amino acid concentration by HPLC. We found that, in VPA rats, glutamate and glutamine concentrations were increased in hippocampus and glycine concentration was increased in cortex. We did not find changes in other regions or in plasma amino acid concentration in the VPA group with respect to control group. Our results suggest that VPA exposure in utero may impair inhibitory and excitatory amino acid transmission in the infant brain.
自闭症谱系障碍与 GABA 能和谷氨酸能神经递质传递的改变有关。在这里，我们旨在确定产前暴露于丙戊酸（VPA）的大鼠脑组织和血浆中 GABA、谷氨酸、谷氨酰胺、天冬氨酸、牛磺酸和甘氨酸的浓度，VPA 是一种公认的自闭症实验模型。怀孕的老鼠在第 12 天胚胎期注射 VPA（600mg/Kg）。对照组老鼠注射生理盐水。在出生后第 14 天，两组（雄性和雌性）的老鼠被麻醉，断头处死，并取出大脑。额叶皮层、海马体、杏仁核、脑干和小脑被解剖并匀浆。匀浆离心后，上清液通过 HPLC 与荧光检测相结合来定量氨基酸浓度。通过心脏穿刺获得血液样本；分离血浆并进行蛋白沉淀，通过 HPLC 定量氨基酸浓度。我们发现，在 VPA 大鼠中，海马体中的谷氨酸和谷氨酰胺浓度增加，而皮质中的甘氨酸浓度增加。与对照组相比，我们未发现 VPA 组其他区域或血浆氨基酸浓度的变化。我们的结果表明，宫内暴露于 VPA 可能会损害婴儿大脑中的抑制性和兴奋性氨基酸传递。
