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



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Partearroyo Cediel, Teresa and Pérez Miguelsanz, Juliana and Peña Melián, Ángel and Maestro de las Casas, Carmen and Úbeda Martín, Natalia and Valera Moreiras, Gregorio (2016) Low and high dietary folic acid levels perturb postnatal cerebellar morphology in growing rats. British journal of nutrition, 115 (11). pp. 1967-1977. ISSN 0007-1145

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Official URL: https://doi.org/10.1017/S0007114516001008


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.

Item Type:Article
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© The Authors 2016
© Cambridge University Press
(Submitted 10 July 2015 – Final revision received 7 February 2016 – Accepted 19 February 2016 – First published online 4 April 2016)

Uncontrolled Keywords:Cerebellum; Cognitive deficits; Corticogenesis; FA folic acid; Folic acid; NTD neural tube defects; Postnatal morphology; Supplementation
Subjects:Medical sciences > Medicine > Anatomy
Medical sciences > Medicine > Neurosciences
Medical sciences > Biology > Animal physiology
ID Code:44371
Deposited On:31 Aug 2017 08:10
Last Modified:04 Sep 2017 11:22

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