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cAMP/PKA/CREB/GLT1 signaling involved in the antidepressant-like effects of phosphodiesterase 4D inhibitor (GEBR-7b) in rats
| Content Provider | Semantic Scholar |
|---|---|
| Author | Guo, Haibiao Sayed, Mohammad Daud Som Lu, Yang Yang, Ting Zhou, Dongsheng Chen, Zhongming Wang, Haitao Wang, Chuang Xu, Jiangping |
| Copyright Year | 2016 |
| Abstract | OBJECTIVES GEBR-7b, a potential phosphodiesterase 4D inhibitor, has been shown to have memory-enhancing effects in rodents. However, it is still unknown whether GEBR-7b also has the antidepressant-like effects in rats. Herein, we examined the potential of GEBR-7b to attenuate depression-like behaviors in the rat model of depression induced by chronic unpredictable stress (CUS). Next, we also investigated the alterations of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA) catalytic subunit (PKAca), cAMP response element-binding (CREB), and glutamate transporter 1 (GLT1) levels produced by GEBR-7b in the rats model of depression. METHODS Effects of GEBR-7b on CUS (35 days)-induced depression-like behaviors were examined by measuring immobility time in the forced swimming test (FST). Hippocampal cAMP levels were examined by enzyme-linked immunosorbent assay, whereas PKAca, phosphorylation of CREB (pCREB), CREB, and GLT1 in the hippocampus of rats were subjected to Western blot analysis. RESULTS CUS exposure caused a depression-like behavior evidenced by the increased immobility time in FST. Depression-like behavior induced by CUS was accompanied by a significant increased GLT, decreased cAMP, PKAca, pCREB activities in hippocampus. However, repeated GEBR-7b administration significantly reversed CUS-induced depression-like behavior and changes of cAMP/PKA/CREB/GLT1 signaling. No alteration was observed in locomotor activity in open field test. CONCLUSION These findings indicate that GEBR-7b reversed the depression-like behaviors induced by CUS in rats, which is at least in part mediated by modulating cAMP, PKAca, pCREB, and GLT1 levels in the hippocampus of rats, supporting its neuroprotective potential against behavioral and biochemical dysfunctions induced by CUS. |
| Starting Page | 219 |
| Ending Page | 227 |
| Page Count | 9 |
| File Format | PDF HTM / HTML |
| DOI | 10.2147/NDT.S90960 |
| PubMed reference number | 26855578 |
| Journal | Medline |
| Volume Number | 12 |
| Alternate Webpage(s) | https://www.dovepress.com/getfile.php?fileID=28732 |
| Alternate Webpage(s) | https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1c/61/ndt-12-219.PMC4725689.pdf |
| Journal | Neuropsychiatric disease and treatment |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
