大脑皮层细胞培养物长期暴露于丙戊酸、地西泮或乙琥胺后的神经化学差异效应。

Differential neurochemical effects of chronic exposure of cerebral cortical cell culture to valproic acid, diazepam, or ethosuximide.

作者信息

Sher P K, Neale E A, Graubard B I, Habig W H, Fitzgerald S C, Nelson P G

机构信息

Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, Bethesda, MD.

出版信息

Pediatr Neurol. 1985 Jul-Aug;1(4):232-7. doi: 10.1016/s0887-8994(85)80007-2.

DOI:10.1016/s0887-8994(85)80007-2

PMID:3939744

Abstract

We have assessed the relative neurochemical effects of valproic acid, ethosuximide, and diazepam on dissociated cultures of mouse cerebral cortex. Cultures were exposed chronically (11 days) to each antiepileptic drug and assayed for number of neurons, total protein, tetanus toxin fixation, high-affinity uptake of gamma-aminobutyric acid and beta-alanine, choline acetyltransferase activity, and specific and clonazepam-displaceable benzodiazepine binding. Ethosuximide-exposed cultures did not evidence neuronal toxicity; exposure to valproic acid and diazepam resulted in modest neuronal toxicity. However, exposure to each of these drugs resulted in a marked reduction in benzodiazepine binding. This effect may relate to a common mechanism of action of drugs used to treat absence seizures.

摘要

我们评估了丙戊酸、乙琥胺和地西泮对小鼠大脑皮质解离培养物的相对神经化学作用。将培养物长期（11天）暴露于每种抗癫痫药物，并检测神经元数量、总蛋白、破伤风毒素固定、γ-氨基丁酸和β-丙氨酸的高亲和力摄取、胆碱乙酰转移酶活性以及特异性和可被氯硝西泮取代的苯二氮䓬结合。暴露于乙琥胺的培养物未显示神经元毒性；暴露于丙戊酸和地西泮导致了适度的神经元毒性。然而，暴露于这些药物中的每一种都会导致苯二氮䓬结合显著减少。这种效应可能与用于治疗失神发作的药物的共同作用机制有关。