Folic acid supplementation during pregnancy alters behavior in male rat offspring: nitrative stress and neuroinflammatory implications

• Published in: Molecular neurobiology Vol. 59; no. 4; pp. 2150 - 2170
• Main Authors: Silveira, Josiane Silva, Ramires Júnior, Osmar Vieira, Schmitz, Felipe, Ferreira, Fernanda Silva, Rodrigues, Fabiana Cristina, Silva, Robson Coutinho, Savio, Luiz Eduardo Baggio, Wyse, Angela T. S.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-04-2022; Springer Nature B.V
• Subjects: Acids; Animals; Anxiety; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cerebral cortex; Diet; Dietary Supplements; Exploratory behavior; Female; Folic acid; Folic Acid - pharmacology; Folic Acid Deficiency - complications; Gene expression; Habituation; Homeostasis; Humans; IL-1β; Inflammation; Interleukin 10; Interleukin 6; Male; Mental depression; Monocyte chemoattractant protein 1; Motor activity; Neurobiology; Neurology; Neurosciences; Nitric-oxide synthase; Offspring; Oxidative stress; Pregnancy; Prenatal Exposure Delayed Effects - metabolism; Rats; Tumor necrosis factor-α; Vitamin B; Oxidative stress; Neuroinflammation; Offspring; Behavior; Nitric oxide; Folic acid
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-022-02724-7

Pregnancy diet can impact offspring’s neurodevelopment, metabolism, redox homeostasis, and inflammatory status. In pregnancy, folate demand is increased due to the requirement for one-carbon transfer reactions. The present study was proposed to investigate the effect of folic acid supplementation throughout pregnancy on a battery of behavior tests (olfactory preference, motor activity, exploratory capacity, habituation, memory, anxiety- and depression-like behavior). Redox homeostasis and neuroinflammatory status in cerebral cortex were also investigated. After pregnancy confirmation, the pregnant rats were randomly divided into two groups, according to the diet: group 1, (control) standard diet (2 mg/kg diet of folic acid) and group 2, supplemented diet with 4 mg/kg diet of folic acid. Throughout the gestational period, the pregnant rats received experimental diets. Results show that the supplemented diet with 4 mg/kg diet of folic acid throughout pregnancy impaired memory and motricity of the offspring when compared with control (standard diet). It was also observed an increase in anxiety- and depression-like behavior in this group. Nitrite levels increased in cerebral cortex of the offspring, when compared to control group. In contrast, iNOS expression and immunocontent were not altered. Moreover, we identify an increase in TNF-α, IL-1β, IL-6, IL-10, and MCP-1 gene expression in the cerebral cortex. In conclusion, our study showed that the supplemented diet with 4 mg/kg diet of folic acid throughout pregnancy may cause behavioral and biochemical changes in the male offspring
Graphical abstract
After pregnancy confirmation, the pregnant rats were randomly divided into two groups, according to the diet: group 1, (control) standard diet (2 mg/kg diet of folic acid) and group 2, supplemented diet with 4 mg/kg diet of folic acid. Throughout the gestational period, the pregnant rats received experimental diets. Results show that folic acid supplementation did not impair the mother–pup relationship. We showed that supplemented diet with 4 mg/kg diet of folic acid during pregnancy impairs memory and motricity of the offspring when compared with standard diet. It was also observed an increase in anxiety- and depression-like behavior in this group. Nitrative stress and neuroinflammation parameters were increased in the cerebral cortex of the offspring. ROS, reactive oxygen species.