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Resveratrol and dimethyl fumarate ameliorate depression-like behaviour in a rat model of chronic unpredictable mild stress.
Brain Res. 2018 12 15; 1701:227-236.BR

Abstract

Chronic stress occurs in everyday life and induces depression. Emerging evidence shows that oxidative stress, inflammation and apoptosis are main contributing pathophysiologic mechanisms of depression. Resveratrol and dimethyl fumarate (DMF) are natural antioxidants that have diverse biological activities. Our study aimed to determine whether resveratrol and DMF affected these systems in rats exposed to chronic unpredictable mild stress (CUMS)-induced depression-like behaviours. Rats were submitted to 8 weeks of CUMS to induce depressive-like behaviour. The depressive-like behaviour of rats induced by CUMS was revealed by an elevated serum corticosterone level and decreased serum and hippocampal serotonin levels. Our results showed that CUMS significantly-induced behavioural abnormalities (reduced sucrose preference and increased immobility time) in stressed rats. CUMS exposure significantly decreased BDNF and β-catenin expression levels as well as increased GSK-3β expression level in hippocampus. Furthermore, CUMS exposure resulted in a significant increase in expression levels of NF-κB, TNF-α and IL-Iβ accompanied by decreased Bcl-2 expression level. CUMS increased hippocampal MDA level and significantly decreased hippocampal GSH and serum total antioxidant capacity levels compared to the control group. Histopathological examinations provided evidence for the biochemical and molecular analysis. All of these effects were significantly ameliorated by administration of resveratrol and DMF. In conclusion, our study revealed that resveratrol and DMF exerted promising antidepressant-like effects in CUMS rats that are mediated in part by suppressing the neuroinflammation, oxidative stress, apoptosis and up-regulating hippocampal BDNF and β-catenin levels. Serum serotonin analysis may be a reliable indicator for monitoring depression.

Authors+Show Affiliations

Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.Department of Biochemistry, Faculty of Pharmacy, October 6 University, Cairo, Egypt.Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Electronic address: nermin.ibrahim@pharma.cu.edu.eg.Department of Biochemistry, Faculty of Pharmacy, October 6 University, Cairo, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30244113

Citation

Abd El-Fattah, Amal Ahmed, et al. "Resveratrol and Dimethyl Fumarate Ameliorate Depression-like Behaviour in a Rat Model of Chronic Unpredictable Mild Stress." Brain Research, vol. 1701, 2018, pp. 227-236.
Abd El-Fattah AA, Fahim AT, Sadik NAH, et al. Resveratrol and dimethyl fumarate ameliorate depression-like behaviour in a rat model of chronic unpredictable mild stress. Brain Res. 2018;1701:227-236.
Abd El-Fattah, A. A., Fahim, A. T., Sadik, N. A. H., & Ali, B. M. (2018). Resveratrol and dimethyl fumarate ameliorate depression-like behaviour in a rat model of chronic unpredictable mild stress. Brain Research, 1701, 227-236. https://doi.org/10.1016/j.brainres.2018.09.027
Abd El-Fattah AA, et al. Resveratrol and Dimethyl Fumarate Ameliorate Depression-like Behaviour in a Rat Model of Chronic Unpredictable Mild Stress. Brain Res. 2018 12 15;1701:227-236. PubMed PMID: 30244113.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Resveratrol and dimethyl fumarate ameliorate depression-like behaviour in a rat model of chronic unpredictable mild stress. AU - Abd El-Fattah,Amal Ahmed, AU - Fahim,Atef Tadros, AU - Sadik,Nermin Abdel Hamid, AU - Ali,Bassam Mohamed, Y1 - 2018/09/20/ PY - 2018/06/18/received PY - 2018/09/15/revised PY - 2018/09/19/accepted PY - 2018/9/24/pubmed PY - 2019/11/5/medline PY - 2018/9/24/entrez KW - Chronic unpredictable mild stress KW - Depression KW - Dimethyl fumarate KW - Oxidative stress KW - Resveratrol SP - 227 EP - 236 JF - Brain research JO - Brain Res. VL - 1701 N2 - Chronic stress occurs in everyday life and induces depression. Emerging evidence shows that oxidative stress, inflammation and apoptosis are main contributing pathophysiologic mechanisms of depression. Resveratrol and dimethyl fumarate (DMF) are natural antioxidants that have diverse biological activities. Our study aimed to determine whether resveratrol and DMF affected these systems in rats exposed to chronic unpredictable mild stress (CUMS)-induced depression-like behaviours. Rats were submitted to 8 weeks of CUMS to induce depressive-like behaviour. The depressive-like behaviour of rats induced by CUMS was revealed by an elevated serum corticosterone level and decreased serum and hippocampal serotonin levels. Our results showed that CUMS significantly-induced behavioural abnormalities (reduced sucrose preference and increased immobility time) in stressed rats. CUMS exposure significantly decreased BDNF and β-catenin expression levels as well as increased GSK-3β expression level in hippocampus. Furthermore, CUMS exposure resulted in a significant increase in expression levels of NF-κB, TNF-α and IL-Iβ accompanied by decreased Bcl-2 expression level. CUMS increased hippocampal MDA level and significantly decreased hippocampal GSH and serum total antioxidant capacity levels compared to the control group. Histopathological examinations provided evidence for the biochemical and molecular analysis. All of these effects were significantly ameliorated by administration of resveratrol and DMF. In conclusion, our study revealed that resveratrol and DMF exerted promising antidepressant-like effects in CUMS rats that are mediated in part by suppressing the neuroinflammation, oxidative stress, apoptosis and up-regulating hippocampal BDNF and β-catenin levels. Serum serotonin analysis may be a reliable indicator for monitoring depression. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/30244113/Resveratrol_and_dimethyl_fumarate_ameliorate_depression_like_behaviour_in_a_rat_model_of_chronic_unpredictable_mild_stress_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(18)30491-8 DB - PRIME DP - Unbound Medicine ER -