Department of Anatomy, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, 05029, Republic of Korea.
Biol Trace Elem Res. 2018 Apr;182(2):278-286. doi: 10.1007/s12011-017-1086-z. Epub 2017 Jul 6.
In the present study, we investigated the effects of ascorbic acid on lead-exposed developing cerebellum. Female rats were divided into the following three groups: control (distilled water), lead (0.2% lead acetate), and lead plus ascorbic acid (100 mg/kg/day, 10% solution). To evaluate the effect of lead exposure and ascorbic acid treatment accurately on the cerebellar development for the gestational period, we halted further treatment with lead and ascorbic acid in the dams after delivery of the pups. Although the ascorbic acid slightly decreased the lead level in pups, lead level was still high in the group treated with lead plus ascorbic acid group compared with the control group. The blood lead levels indicated that the ascorbic acid could facilitate both the excretion and transfer of lead from a dam to its pups via milk. At postnatal day 21, lead exposure significantly reduced the number of Purkinje cells in the cerebellar cortex of pups. Additionally, lead treatment induced degenerative changes such as reduction of glutamic acid decarboxylase (GAD67) and c-kit expressions are observed in the developing cerebellar cortex. In the cerebellum of the pups from the lead plus ascorbic acid group, reduction of the number of Purkinje cells, GAD67 expression, and c-kit immunopositivity were remarkably restored compared with the lead group. Our present results suggested that ascorbic acid treatment to lead-exposed dam exerted protective effects on the developing cerebellum against lead-induced neurotoxicity.
在本研究中，我们研究了抗坏血酸对暴露于铅的发育中小脑的影响。雌性大鼠分为以下三组：对照组（蒸馏水）、铅组（0.2%醋酸铅）和铅加抗坏血酸组（100mg/kg/天，10%溶液）。为了准确评估铅暴露和抗坏血酸处理对妊娠期小脑发育的影响，我们在幼崽出生后停止了对母鼠的进一步铅和抗坏血酸治疗。尽管抗坏血酸略微降低了幼崽体内的铅水平，但与对照组相比，铅加抗坏血酸组的铅水平仍然很高。血液铅水平表明，抗坏血酸可以促进铅从母体向幼崽通过乳汁的排泄和转移。在出生后第 21 天，铅暴露显著减少了幼崽小脑皮质浦肯野细胞的数量。此外，铅处理诱导了发育中小脑皮质中谷氨酸脱羧酶（GAD67）和 c-kit 表达的退行性变化。在铅加抗坏血酸组幼崽的小脑内，与铅组相比，浦肯野细胞数量、GAD67 表达和 c-kit 免疫阳性的减少明显得到恢复。我们的研究结果表明，抗坏血酸处理暴露于铅的母鼠对发育中的小脑具有保护作用，可防止铅诱导的神经毒性。
