title: Vitamin C Deficiency Causes Severe Defects in the Development of the Neonatal Cerebellum and in the Motor Behaviors of Gulo(-/-) Mice.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Hyemin
authors.initials: H
authors.lastname: Kim
authors.affiliation: 1 Laboratory of Immunology and Vitamin C, Department of Anatomy, Seoul National University College of Medicine , Seoul, Republic of Korea.
authors.forename: Yejin
authors.initials: Y
authors.lastname: Kim
authors.affiliation: 1 Laboratory of Immunology and Vitamin C, Department of Anatomy, Seoul National University College of Medicine , Seoul, Republic of Korea.
authors.forename: Seyeon
authors.initials: S
authors.lastname: Bae
authors.affiliation: 3 Institute for Experimental Animals, Seoul National University College of Medicine , Seoul, Republic of Korea.
authors.forename: Seung Hyeon
authors.initials: SH
authors.lastname: Lim
authors.affiliation: 1 Laboratory of Immunology and Vitamin C, Department of Anatomy, Seoul National University College of Medicine , Seoul, Republic of Korea.
authors.forename: Mirim
authors.initials: M
authors.lastname: Jang
authors.affiliation: 1 Laboratory of Immunology and Vitamin C, Department of Anatomy, Seoul National University College of Medicine , Seoul, Republic of Korea.
authors.forename: Jiyea
authors.initials: J
authors.lastname: Choi
authors.affiliation: 1 Laboratory of Immunology and Vitamin C, Department of Anatomy, Seoul National University College of Medicine , Seoul, Republic of Korea.
authors.forename: Jane
authors.initials: J
authors.lastname: Jeon
authors.affiliation: 1 Laboratory of Immunology and Vitamin C, Department of Anatomy, Seoul National University College of Medicine , Seoul, Republic of Korea.
authors.forename: Young-il
authors.initials: YI
authors.lastname: Hwang
authors.affiliation: 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.
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Kang
authors.affiliation: 1 Laboratory of Immunology and Vitamin C, Department of Anatomy, Seoul National University College of Medicine , Seoul, Republic of Korea.
authors.forename: Wang Jae
authors.initials: WJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001205:Ascorbic Acid / Q000378:metabolism; D001206:Ascorbic Acid Deficiency / Q000150:complications*; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism* / Q000503:physiopathology*; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000378:metabolism; D020300:Intracranial Hemorrhages / Q000209:etiology / Q000473:pathology; D050544:L-Gulonolactone Oxidase / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics*; D065886:Neurodevelopmental Disorders / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D018384:Oxidative Stress; D050497:Stillbirth; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D050544:L-Gulonolactone Oxidase; D001205:Ascorbic Acid