Kim Hyemin, Kim Yejin, Bae Seyeon, Lim Seung Hyeon, Jang Mirim, Choi Jiyea, Jeon Jane, Hwang Young-il, Kang Jae Seung, Lee Wang Jae
1 Laboratory of Immunology and Vitamin C, Department of Anatomy, Seoul National University College of Medicine , Seoul, Republic of Korea.
2 Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Republic of Korea.
Antioxid Redox Signal. 2015 Dec 1;23(16):1270-83. doi: 10.1089/ars.2014.6043. Epub 2015 Jun 17.
The developing brain of a neonate is particularly susceptible to damage by vitamin C deficiency because of its rapid growth and immature antioxidant system. Cognitive impairment and sensory motor deficits are found in the adult brain upon vitamin C deficiency. Therefore, the aim of this study was to clarify the role of vitamin C in its own right and its related mechanisms in Gulo(-/-) mice incapable of synthesizing vitamin C.
When vitamin C supplementation was ceased for 2 weeks until delivery, stillbirths and a significant reduction in neonatal mice were observed and the growth of neonates was remarkably decreased. In addition, intraparenchymal hemorrhages were found in most of the brains, especially in the stillborn neonates. In addition, the levels of malondialdehyde (MDA) and 8-isoprostanes were increased and structural abnormalities were found in the cortex, hippocampus, and cerebellum. Especially, vitamin C deficiency caused the failure of or a delay in the formation of cerebellar fissures accompanied by abnormal foliation and altered Purkinje cell alignment. In the developed adult brains from vitamin C-deficient Gulo(-/-) mice, the levels of glutathione, MDA, nitrate, IL-6, TNF-α, and Bax were increased and the expression of the GABRA6 and calbindin-28k was decreased. Due to atrophy of the granule and Purkinje cells, the motor behavior of vitamin C-deficient Gulo(-/-) mice declined.
Vitamin C deficiency during gestation induces intraparenchymal hemorrhages and severe defects in the development of the cerebellum. In fully developed brains, it induces the functional impairment by altering the cellular composition in the cerebellum.
新生儿发育中的大脑因其快速生长和未成熟的抗氧化系统，特别容易受到维生素C缺乏的损害。维生素C缺乏会导致成年大脑出现认知障碍和感觉运动缺陷。因此，本研究的目的是阐明维生素C本身及其相关机制在无法合成维生素C的Gulo(-/-)小鼠中的作用。
当在分娩前2周停止补充维生素C时，观察到死产和新生小鼠数量显著减少，新生儿的生长明显下降。此外，在大多数大脑中发现了脑实质内出血，尤其是在死产新生儿中。此外，丙二醛（MDA）和8-异前列腺素水平升高，在皮质、海马和小脑中发现结构异常。特别是，维生素C缺乏导致小脑裂形成失败或延迟，伴有叶状异常和浦肯野细胞排列改变。在维生素C缺乏的Gulo(-/-)小鼠发育成熟的成年大脑中，谷胱甘肽、MDA、硝酸盐、白细胞介素-6、肿瘤坏死因子-α和Bax水平升高，GABRA6和钙结合蛋白-28k的表达降低。由于颗粒细胞和浦肯野细胞萎缩，维生素C缺乏的Gulo(-/-)小鼠的运动行为下降。
妊娠期维生素C缺乏会诱发脑实质内出血和小脑发育的严重缺陷。在完全发育的大脑中，它会通过改变小脑中的细胞组成来诱发功能障碍。
