title: Low and high dietary folic acid levels perturb postnatal cerebellar morphology in growing rats.
abstract: The brain is particularly sensitive to folate metabolic disturbances, because methyl groups are critical for brain functions. This study aimed to investigate the effects of different dietary levels of folic acid (FA) on postnatal cerebellar morphology, including the architecture and organisation of the various layers. A total of forty male OFA rats (a Sprague-Dawley strain), 5 weeks old, were classified into the following four dietary groups: FA deficient (0 mg/kg FA); FA supplemented (8 mg/kg FA); FA supra-supplemented (40 mg/kg FA); and control (2 mg/kg FA) (all n 10 per group). Rats were fed ad libitum for 30 d. The cerebellum was quickly removed and processed for histological and immunohistochemical analysis. Slides were immunostained for glial fibrillary acidic protein (to label Bergmann glia), calbindin (to label Purkinje cells) and NeuN (to label post-mitotic neurons). Microscopic analysis revealed two types of defect: partial disappearance of fissures and/or neuronal ectopia, primarily in supra-supplemented animals (incidence of 80 %, P≤0·01), but also in deficient and supplemented groups (incidence of 40 %, P≤0·05), compared with control animals. The primary fissure was predominantly affected, sometimes accompanied by defects in the secondary fissure. Our findings show that growing rats fed an FA-modified diet, including both deficient and supplemented diets, have an increased risk of disturbances in cerebellar corticogenesis. Defects caused by these diets may have functional consequences in later life. The present study is the first to demonstrate that cerebellar morphological defects can arise from deficient, as well as high, FA levels in the diet.
authors.affiliation: 1Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia,Universidad CEU San Pablo,Boadilla del Monte,28668 Madrid,Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Partearroyo
authors.affiliation: 2Departamento de Anatomía y Embriología Humanas, Facultad de Medicina,Universidad Complutense,28040 Madrid,Spain.
authors.forename: Juliana
authors.initials: J
authors.lastname: Pérez-Miguelsanz
authors.affiliation: 2Departamento de Anatomía y Embriología Humanas, Facultad de Medicina,Universidad Complutense,28040 Madrid,Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Peña-Melián
authors.affiliation: 2Departamento de Anatomía y Embriología Humanas, Facultad de Medicina,Universidad Complutense,28040 Madrid,Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Maestro-de-Las-Casas
authors.affiliation: 1Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia,Universidad CEU San Pablo,Boadilla del Monte,28668 Madrid,Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Úbeda
authors.affiliation: 1Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia,Universidad CEU San Pablo,Boadilla del Monte,28668 Madrid,Spain.
authors.forename: Gregorio
authors.initials: G
authors.lastname: Varela-Moreiras
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D001927:Brain Diseases / Q000209:etiology*; D002531:Cerebellum / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D004032:Diet; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005492:Folic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D005494:Folic Acid Deficiency / Q000150:complications; D008297:Male; D009752:Nutritional Status; D017207:Rats, Sprague-Dawley; D014803:Vitamin B Complex / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D014803:Vitamin B Complex; D005492:Folic Acid
keywords: Cerebellum; Cognitive deficits; Corticogenesis; FA folic acid; Folic acid; NTD neural tube defects; Postnatal morphology; Supplementation