Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 554, Issue -, Pages 107-113Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2021.03.104
Keywords
Post-stroke depression; Gadd45b; Neuroinflammation; BDNF
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Funding
- National Natural Science Foundation of China [81601018, 82000771]
- Shandong Provincial Natural Science Foundation [ZR2019PH017]
- Jinan Municipal Science and Technology Project [201805073]
- China Postdoctoral Science Foundation [2017M622217]
- Academic promotion programme of Shandong First Medical University [2019QL013]
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This study demonstrated the antidepressant effects of Gadd45b after cerebral ischemia and its mechanisms involving the BDNF-ERK-CREB pathway and neuroinflammation.
Background: Poststroke depression (PSD) is an important consequence after stroke, with a negative impact on stroke outcome. Recent evidence points to a modulatory role of Growth arrest and DNA damage-inducible protein 45 beta (Gadd45b) in depression. Herein, we evaluated the antidepressant efficacy and mechanism underlying the potent therapeutic effects of Gadd45b after cerebral ischemia. Methods: Adult male Sprague-Dawley rats were subjected to cerebral ischemia by permanent middle cerebral artery occlusion (MCAO). The sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST) were performed after completing MCAO to study the antidepressant-like effects. The expression of brain-derived neurotrophic factor (BDNF) and neuroinflammation were determined in the hippocampus. Results: We showed that Gadd45b knockdown induced depression-like behaviors after cerebral ischemia, including increased immobility time in the FST and TST and reduced sucrose preference. Gadd45b knockdown enhanced the expression of pro-inflammatory cytokines IL-6 and TNF-a, accompanying with decreased protein levels of BDNF in the hippocampus. Moreover, the levels of phosphorylated ERK and CREB, which have been implicated in events downstream of BDNF signaling, were also decreased after cerebral ischemia. Conclusion: Hence, the results showed that Gadd45b is a promising drug candidate for treating PSD and possibly other nervous system diseases associated with neuroinflammation. Gadd45b may have therapeutic potential for PSD through BDNF-ERK-CREB pathway and neuroinflammation. (C) 2021 Elsevier Inc. All rights reserved.
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