Low and high dietary folic acid levels perturb postnatal cerebellar morphology in growing rats

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...

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Detalles Bibliográficos
Autores: Partearroyo Cediel, Teresa, Pérez De Miguelsanz, María Juliana, Peña Melián, Ángel, Maestro De Las Casas, María Del Carmen, Úbeda Martín, Natalia, Valera Moreiras, Gregorio
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/23406
Acceso en línea:https://hdl.handle.net/20.500.14352/23406
Access Level:acceso abierto
Palabra clave:577.164.17
611.817.1
Cerebellum
Cognitive deficits
Corticogenesis
FA folic acid
Folic acid
NTD neural tube defects
Postnatal morphology
Supplementation
Anatomía
Neurociencias (Medicina)
Fisiología animal (Biología)
2410.02 Anatomía Humana
2490 Neurociencias
2401.13 Fisiología Animal
Descripción
Sumario: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.