L'acide folique améliore le comportement anormal via l'atténuation du stress oxydatif, de l'inflammation et de la ferroptose chez la souris BTBR T + tf / J modèle de l'autisme

Aperçu: G.M.

Le but de cette étude était d'examiner les effets de l'acide folique (FA) sur les phénotypes autistiques chez des souris BTBR T + Itpr3tf / J (BTBR) et d'étudier les mécanismes sous-jacents. Les souris ont reçu de la FA (0,2 mg / kg / jour) par voie orale des jours postnatals 14 à 35. 

La supplémentation orale de FA à des souris BTBR a permis de récupérer des comportements stéréotypés et répétitifs, un déficit social et des altérations de l’apprentissage et de la mémoire dans l’espace, probablement en améliorant le stress oxydatif et les réponses inflammatoires en modifiant les voies de signalisation de la ferroptose.

J Nutr Biochem. 2019 Jun 18;71:98-109. doi: 10.1016/j.jnutbio.2019.05.002.

Folic acid improves abnormal behavior via mitigation of oxidative stress, inflammation, and ferroptosis in the BTBR T+ tf/J mouse model of autism

Zhang Q¹, Wu H², Zou M³, Li L³, Li Q³, Sun C³, Xia W³, Cao Y⁴, Wu L⁵.

Author information

1

Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, China; Department of Nursing, Daqing campus of Harbin Medical University, Daqing, Heilongjiang, China.

2

Department of Nursing, Daqing campus of Harbin Medical University, Daqing, Heilongjiang, China.

3

Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, China.

4

Department of Pharmacology, Daqing campus of Harbin Medical University, Daqing, Heilongjiang, China. Electronic address: 437343482@qq.com.

5

Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, China. Electronic address: wulijiehyd@126.com.

Abstract

The aim of this study was to examine the effects of folic acid (FA) on the autistic phenotypes in BTBR T+ Itpr3tf/J (BTBR) mice and to investigate underlying mechanisms. Mice received FA (0.2 mg/kg/day) orally from postnatal days 14 to 35. Mice were then tested for stereotyped and repetitive behaviors, social interaction, and spatial learning and memory at the end of FA supplementation. Oxidative stress, neuroinflammatory responses and ferroptosis-related proteins in the brain were also evaluated. FA supplementation in BTBR mice reduced repetitive and stereotyped behavior, improved social communication, and enhanced memory and spatial learning. FA supplementation also reduced neuronal loss in hippocampal CA1 regions of the brain and decreased the levels of the proinflammatory cytokines such as interleukin-1β (IL-1β), Iba-1, IL-18, tumor necrosis factor-a, and IL-6 and glial fibrillary acidic protein in the hippocampus. FA supplementation changed the malondialdehyde and glutathione levels and superoxide dismutase (SOD) and glutathione peroxidase activities in the hippocampus. FA supplementation inhibited the elevation of the SOD1 and TFR protein levels and enhanced the relative expression levels of glutathione peroxidase 4 and ferroportin 1 in the hippocampus and increased the relative levels of phospho-Ca2+/calmodulin-dependent protein kinase II and phospho-cAMP-response element binding protein in the hippocampus. FA oral supplementation to BTBR mice rescued stereotyped and repetitive behaviors, social deficit, and spatial learning and memory impairments, likely by improving the oxidative-stress and inflammatory responses by altering the ferroptosis signaling pathways.

Copyright © 2019. Published by Elsevier Inc.

PMID:31323609

DOI:10.1016/j.jnutbio.2019.05.002