title: Vitamin C Depletion in Prenatal Guinea Pigs as a Model of Lissencephaly Type II.
abstract: Humans and guinea pigs are unable to produce vitamin C, with deficiency resulting in a well-known disorder of collagen synthesis. Pial basement membrane structure preservation is essential in the proper migration of neurons. In our study, intrauterine deprivation of vitamin C in guinea pig fetuses led to a collagen synthesis disorder, weakness, and finally a breach of pial basement membrane. We found excessive migration of the external germinal layer cells into the subarachnoid space of the cerebellum through defects in the pial basement membrane. The changes ranged from focal rupture of pial basement membranes to their complete disintegration. The loss of proper folia formation resulted in macroscopically visible flattening of the cerebellar surface. Different grades of dysplastic changes in the folia of the cerebellar cortex were observed in 2 experimental groups assigned different limits to mark the time of commencement and duration of vitamin C deprivation. The most severe form of dysplastic changes was characterized by marked irregularity of the cerebellar cortex similar to that in lissencephaly type II. Thus, prenatal vitamin C deficiency represents a novel animal model to study the effects of collagen synthesis on development of breaches in the pial basement membrane, disordered migration of neurons, dysplasia of cerebellar cortex, and the pathogenesis of lissencephaly.
authors.affiliation: Department of Histology and Embryology, Medical Faculty, Novi Sad, Vojvodina, Serbia capo.ivan@gmail.com.
authors.forename: I
authors.initials: I
authors.lastname: Čapo
authors.affiliation: Department of Histology and Embryology, Medical Faculty, Novi Sad, Vojvodina, Serbia.
authors.forename: N
authors.initials: N
authors.lastname: Hinić
authors.affiliation: Department of Histology and Embryology, Medical Faculty, Novi Sad, Vojvodina, Serbia.
authors.forename: D
authors.initials: D
authors.lastname: Lalošević
authors.affiliation: Department of Pathology, Medical Faculty, Novi Sad, Vojvodina, Serbia.
authors.forename: N
authors.initials: N
authors.lastname: Vučković
authors.affiliation: Department of Pharmacology and Toxicology, Medical Faculty, Novi Sad, Vojvodina, Serbia.
authors.forename: N
authors.initials: N
authors.lastname: Stilinović
authors.affiliation: Department of Psychiatry, Medical Faculty, Clinical Center of Vojvodina, Novi Sad, Serbia.
authors.forename: J
authors.initials: J
authors.lastname: Marković
authors.affiliation: Department of Neurology, Medical Faculty, Clinical Center of Vojvodina, Novi Sad, Serbia.
authors.forename: S
authors.initials: S
authors.lastname: Sekulić
mesh_terms: D000818:Animals; D001206:Ascorbic Acid Deficiency / Q000473:pathology / Q000662:veterinary*; D001485:Basement Membrane / Q000473:pathology; D002531:Cerebellum / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D054082:Lissencephaly / Q000473:pathology / Q000662:veterinary*; D008297:Male; D009474:Neurons / Q000473:pathology; D012614:Scurvy / Q000473:pathology / Q000662:veterinary
chemical_list: D003094:Collagen
keywords: animal model; cerebellum; guinea pigs; lissencephaly; scurvy; vitamin c deficiency