Antidepressant-Like Effects of Low- and High-Molecular Weight FGF-2 on Chronic Unpredictable Mild Stress Mice
The occurrence of depressive disorder has long been attributed to changes in monoamines, with the focus of drug treatment strategies being to change the effectiveness of monoamines. However, the success achieved by changing these processes is limited and further stimulates the exploration of alterna...
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Frontiers Media S.A.
2018-10-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2018.00377/full |
| _version_ | 1811344891522842624 |
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| author | Lin Wang Xi-Xi Li Xi Chen Xiao-Yan Qin Elissavet Kardami Yong Cheng |
| author_facet | Lin Wang Xi-Xi Li Xi Chen Xiao-Yan Qin Elissavet Kardami Yong Cheng |
| author_sort | Lin Wang |
| collection | DOAJ |
| description | The occurrence of depressive disorder has long been attributed to changes in monoamines, with the focus of drug treatment strategies being to change the effectiveness of monoamines. However, the success achieved by changing these processes is limited and further stimulates the exploration of alternative mechanisms and treatments. Fibroblast growth factor 2 (FGF-2), which occurs in a high-molecular weight (HMW) and low-molecular weight (LMW) form, is a potent developmental modulator and nervous system regulator that has been suggested to play an important role in various psychiatric disorders. In this study, we investigated the antidepressant effects of HMW and LMW FGF-2 on depression induced by chronic stress. Both peripheral LMW and HMW FGF-2 attenuated the depression-like behaviors in chronic unpredictable mild stress (CUMS) mice to a similar extent, as determined by the forced swimming, tail suspension, and sucrose preference tests. We then showed that CUMS-induced oxidative stresses in mice were inhibited by FGF-2 treatments both in central and peripheral. We also showed that both forms of FGF-2 increased the phosphorylation of ERK and AKT, increased Bcl-2 expression and inhibited caspase-3 activation in CUMS mice. Interestingly, HMW FGF-2 enhanced the activity of the brain-derived neurotrophic factor (BDNF) to a greater extent than did LMW FGF-2 in the hippocampus. Taken together, these results suggest that depressive symptoms can be relieved by administering different forms of FGF-2 peripherally in a CUMS-induced depression model through a similar antidepressant signaling pathway, therefore suggesting a potential clinical use for FGF-2 as a treatment for depression. |
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| spelling | doaj.art-bb16da0bc4d6453baacb779726f586b72022-12-22T02:32:22ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-10-011110.3389/fnmol.2018.00377399982Antidepressant-Like Effects of Low- and High-Molecular Weight FGF-2 on Chronic Unpredictable Mild Stress MiceLin Wang0Xi-Xi Li1Xi Chen2Xiao-Yan Qin3Elissavet Kardami4Yong Cheng5Key Laboratory of Ethnomedicine for Ministry of Education, Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, ChinaKey Laboratory of Ethnomedicine for Ministry of Education, Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, ChinaSchool of Pharmacy, Minzu University of China, Beijing, ChinaKey Laboratory of Ethnomedicine for Ministry of Education, Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, ChinaInstitute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Centre, University of Manitoba, Winnipeg, MB, CanadaKey Laboratory of Ethnomedicine for Ministry of Education, Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing, ChinaThe occurrence of depressive disorder has long been attributed to changes in monoamines, with the focus of drug treatment strategies being to change the effectiveness of monoamines. However, the success achieved by changing these processes is limited and further stimulates the exploration of alternative mechanisms and treatments. Fibroblast growth factor 2 (FGF-2), which occurs in a high-molecular weight (HMW) and low-molecular weight (LMW) form, is a potent developmental modulator and nervous system regulator that has been suggested to play an important role in various psychiatric disorders. In this study, we investigated the antidepressant effects of HMW and LMW FGF-2 on depression induced by chronic stress. Both peripheral LMW and HMW FGF-2 attenuated the depression-like behaviors in chronic unpredictable mild stress (CUMS) mice to a similar extent, as determined by the forced swimming, tail suspension, and sucrose preference tests. We then showed that CUMS-induced oxidative stresses in mice were inhibited by FGF-2 treatments both in central and peripheral. We also showed that both forms of FGF-2 increased the phosphorylation of ERK and AKT, increased Bcl-2 expression and inhibited caspase-3 activation in CUMS mice. Interestingly, HMW FGF-2 enhanced the activity of the brain-derived neurotrophic factor (BDNF) to a greater extent than did LMW FGF-2 in the hippocampus. Taken together, these results suggest that depressive symptoms can be relieved by administering different forms of FGF-2 peripherally in a CUMS-induced depression model through a similar antidepressant signaling pathway, therefore suggesting a potential clinical use for FGF-2 as a treatment for depression.https://www.frontiersin.org/article/10.3389/fnmol.2018.00377/fullHMW FGF-2LMW FGF-2depressionoxidative stressAKTERK |
| spellingShingle | Lin Wang Xi-Xi Li Xi Chen Xiao-Yan Qin Elissavet Kardami Yong Cheng Antidepressant-Like Effects of Low- and High-Molecular Weight FGF-2 on Chronic Unpredictable Mild Stress Mice Frontiers in Molecular Neuroscience HMW FGF-2 LMW FGF-2 depression oxidative stress AKT ERK |
| title | Antidepressant-Like Effects of Low- and High-Molecular Weight FGF-2 on Chronic Unpredictable Mild Stress Mice |
| title_full | Antidepressant-Like Effects of Low- and High-Molecular Weight FGF-2 on Chronic Unpredictable Mild Stress Mice |
| title_fullStr | Antidepressant-Like Effects of Low- and High-Molecular Weight FGF-2 on Chronic Unpredictable Mild Stress Mice |
| title_full_unstemmed | Antidepressant-Like Effects of Low- and High-Molecular Weight FGF-2 on Chronic Unpredictable Mild Stress Mice |
| title_short | Antidepressant-Like Effects of Low- and High-Molecular Weight FGF-2 on Chronic Unpredictable Mild Stress Mice |
| title_sort | antidepressant like effects of low and high molecular weight fgf 2 on chronic unpredictable mild stress mice |
| topic | HMW FGF-2 LMW FGF-2 depression oxidative stress AKT ERK |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2018.00377/full |
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