Mercugliano M, Hyman S L, Batshaw M L
Division of Child Development and Rehabilitation, Children's Hospital of Philadelphia, PA 19104.
Pediatrics. 1990 Mar;85(3 Pt 2):432-6.
Methylazoxymethanol, a short-acting antimitotic agent, produces marked cortical hypoplasia in fetuses when injected into pregnant rats. These offspring also have increased cortical concentrations of biogenic amines associated with hyperactivity and learning deficits. In this experiment, rats with a relatively mild degree of methylazoxymethanol-induced cortical hypoplasia were studied to determine whether these neurochemical and behavioral abnormalities persisted. Sprague-Dawley pregnant rats were injected intraperitoneally on day 15 of gestation with methylazoxymethanol acetate (25 mg/kg). Total brain weight was reduced by 12% and cortical slab weight by 28% in methylazoxymethanol-exposed offspring. They were more active than control rats and showed a trend toward slower learning in a swim maze. Affected offspring had increased cortical concentrations of norepinephrine, 5-hydroxyindoleacetic acid, and glycine. There was no significant difference in the concentrations of serotonin gamma-aminobutyric acid, aspartic acid, glutamic acid, or glutamine. Methylazoxymethanol-lesioned animals with mild cortical hypoplasia remained measurably hyperactive and may serve as a model for the study of neurotransmitter and neuropathologic abnormalities associated with hyperactivity in children with microcephaly.
甲基偶氮甲醇是一种短效抗有丝分裂剂，给怀孕大鼠注射后会使胎儿出现明显的皮质发育不全。这些后代的皮质中与多动和学习缺陷相关的生物胺浓度也会增加。在本实验中，对甲基偶氮甲醇诱导的皮质发育不全程度相对较轻的大鼠进行研究，以确定这些神经化学和行为异常是否持续存在。在妊娠第15天，给斯普拉格-道利怀孕大鼠腹腔注射乙酸甲基偶氮甲醇（25毫克/千克）。暴露于甲基偶氮甲醇的后代的全脑重量减少了12%，皮质板重量减少了28%。它们比对照大鼠更活跃，在游泳迷宫中学习速度有变慢的趋势。受影响的后代皮质中去甲肾上腺素、5-羟吲哚乙酸和甘氨酸的浓度增加。血清素、γ-氨基丁酸、天冬氨酸、谷氨酸或谷氨酰胺的浓度没有显著差异。患有轻度皮质发育不全的甲基偶氮甲醇损伤动物仍有明显的多动，可作为研究与小头畸形儿童多动相关的神经递质和神经病理异常的模型。
