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| Content Provider | Springer Nature Link |
|---|---|
| Author | Cunha, Mauricio P. Budni, Josiane Ludka, Fabiana K. Pazini, Francis L. Rosa, Julia Macedo Oliveira, Ágatha Lopes, Mark W. Tasca, Carla I. Leal, Rodrigo B. Rodrigues, Ana Lúcia S. |
| Copyright Year | 2015 |
| Abstract | Creatine has been proposed to exert beneficial effects in the management of depression, but the cell signaling pathways implicated in its antidepressant effects are not well established. This study investigated the involvement of PI3K/Akt signaling pathway and its downstream intracellular targets in the antidepressant-like effect of creatine. The acute treatment of mice with creatine (1 mg/kg, po) increased the Akt and P70S6K phosphorylation, and HO-1, GPx and PSD95 immunocontents. The pretreatment of mice with LY294002 (10 nmol/mouse, icv, PI3K inhibitor), wortmannin (0.1 μg/mouse, icv, PI3K inhibitor), ZnPP (10 μg/mouse, icv, HO-1 inhibitor), or rapamycin (0.2 nmol/mouse, icv, mTOR inhibitor) prevented the antidepressant-like effect of creatine (1 mg/kg, po) in the TST. In addition, the administration of subeffective dose of either the selective GSK3 inhibitor AR-A014418 (0.01 μg/mouse, icv), the nonselective GSK3 inhibitor lithium chloride (10 mg/kg, po), or the HO-1 inductor CoPP (0.01 μg/mouse, icv), in combination with a subeffective dose of creatine (0.01 mg/kg, po) reduced the immobility time in the TST as compared with either drug alone. No treatment caused significant changes in the locomotor activity of mice. These results indicate that the antidepressant-like effect of creatine in the TST depends on the activation of Akt, Nrf2/HO-1, GPx, and mTOR, and GSK3 inhibition. |
| Starting Page | 2954 |
| Ending Page | 2968 |
| Page Count | 15 |
| File Format | |
| ISSN | 08937648 |
| Journal | Molecular Neurobiology |
| Volume Number | 53 |
| Issue Number | 5 |
| e-ISSN | 15591182 |
| Language | English |
| Publisher | Springer US |
| Publisher Date | 2015-05-06 |
| Publisher Place | New York |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Antidepressant Akt Creatine Glycogen kinase 3 Heme oxygenase-1 mTOR Neurosciences Neurobiology Cell Biology Neurology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neurology Cellular and Molecular Neuroscience |
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