Folic acid prevents habituation memory impairment and oxidative stress in an aging model induced by D-galactose

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ORIGINAL ARTICLE

Folic acid prevents habituation memory impairment and oxidative stress in an aging model induced by D-galactose Michelle Lima Garcez 1 & Ricardo Chiengo Sapalo Cassoma 2 & Francielle Mina 2 & Tatiani Bellettini-Santos 2 & Aline Pereira da Luz 2 & Gustavo Luis Schiavo 2 & Eduarda Behenck Medeiros 2 & Ana Carolina Brunatto Falchetti Campos 2 & Sabrina da Silva 2 & Lisienny Campoli Tono Rempel 2 & Amanda Valnier Steckert 3 & Tatiana Barichello 3,4,5,6 & Josiane Budni 2 Received: 10 August 2020 / Accepted: 13 November 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract The present study aimed to evaluate the effect of folic acid treatment in an animal model of aging induced by D-galactose (D-gal). For this propose, adult male Wistar rats received D-gal intraperitoneally (100 mg/kg) and/or folic acid orally (5 mg/kg, 10 mg/kg or 50 mg/kg) for 8 weeks. D-gal caused habituation memory impairment, and folic acid (10 mg/kg and 50 mg/kg) reversed this effect. However, folic acid 50 mg/kg per se caused habituation memory impairment. D-gal increased the lipid peroxidation and oxidative damage to proteins in the prefrontal cortex and hippocampus from rats. Folic acid (5 mg/kg, 10 mg/kg, or 50 mg/kg) partially reversed the oxidative damage to lipids in the hippocampus, but not in the prefrontal cortex, and reversed protein oxidative damage in the prefrontal cortex and hippocampus. D-gal induced synaptophysin and BCL-2 decrease in the hippocampus and phosphorylated tau increase in the prefrontal cortex. Folic acid was able to reverse these D-gal-related alterations in the protein content. The present study shows folic acid supplementation as an alternative during the aging to prevent cognitive impairment and brain alterations that can cause neurodegenerative diseases. However, additional studies are necessary to elucidate the effect of folic acid in aging. Keywords D-galactose . Folic acid . Aging . Cognitive impairment . Oxidative damage . Rats

Introduction * Josiane Budni [email protected] 1

Department of Biochemistry, Federal University of Santa Catarina (UFSC), Florianópolis, Santa Catarina, Brazil

2

Laboratory of Experimental Neurology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC 88806-000, Brazil

3

Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina, Criciúma, SC, Brazil

4

Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX, USA

5

Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX, USA

6

Neuroscience Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX, USA

D-galactose (D-gal) is a reducing sugar that at high levels forms advanced