scholarly journals MicroRNA-124 Attenuates PTSD-like Behaviors and Reduces the Level of Inflammatory Cytokines by Downregulating the Expression of TRAF6 in the Hippocampus of Rats Following Single-prolonged Stress

Author(s):  
Yao Chen ◽  
Lei Tong ◽  
Peng-Yin Nie ◽  
Yu-Lu Chen ◽  
Lili Ji

Abstract BackgroundMicroRNA-124-3p (miR-124) plays an important role in neuroprotective functions in various neurological disorders, but whether miR-124 participates in the pathological progression of posttraumatic stress disorder (PTSD) remains poorly understood. MethodsIn the present study, we evaluated the level of neuroinflammation in the hippocampus of rats exposed to single-prolonged stress (SPS) by western blot and immunofluorescence staining, while the effect of miR-124 on PTSD-like behaviors was evaluated by behavioral test. ResultsOur results demonstrated that the level of miR-124 in the hippocampus of rats exposed to SPS was downregulated and that the upregulation of miR-124 could alleviate the PTSD-like behaviors of SPS rats. This effect of miR-124 might be achieved through TNF receptor-associated Factor 6 (TRAF6), which is a target gene of miR-124 and plays an important role in the immune and inflammatory reaction by regulating nuclear factor kappa-B (NF-κB). Furthermore, we found that miR-124 not only decreased the level of proinflammatory cytokines but also increased the expression levels of synaptic proteins (PSD95 and synapsin I) and regulated the morphology of neurons. ConclusionThese results suggested that miR-124 might attenuate PTSD-like behaviors and decrease the level of proinflammatory cytokines by downregulating the expression of TRAF6 in the hippocampus of rats exposed to SPS.

2020 ◽  
Vol 34 (7) ◽  
pp. 726-736 ◽  
Author(s):  
Yirong Yuan ◽  
Linlin Zhen ◽  
Zhi Li ◽  
Wenhua Xu ◽  
Huilin Leng ◽  
...  

Background: trans-Resveratrol has been extensively investigated for its anti-inflammatory, antioxidant, and anti-psychiatric properties. However, whether it could rescue posttraumatic stress disorder-like stress-induced pain abnormality is unknown. Aim: The present study examined the effects of trans-resveratrol on anxiety-like behavior and neuropathic pain induced by single-prolonged stress, which is a classical animal model for mimicking posttraumatic stress disorder. Methods: The single-prolonged stress-induced anxiety-like behavior and pain response were detected by the novelty suppressed feeding, marble burying, locomotor activity, von Frey, and acetone-induced cold allodynia tests in mice. The serum corticosterone levels and glucocorticoid receptor, protein kinase A, phosphorylated cAMP response element binding protein, and brain-derived neurotrophic factor expression were detected by enzyme-linked immunosorbent assay and immunoblot analyses. Results: trans-Resveratrol reversed single-prolonged stress-induced increased latency to feed and the number of marbles buried in the novelty suppressed feeding and marble burying tests, but did not significantly influence locomotion distance in the locomotor activity test. trans-Resveratrol also reversed single-prolonged stress-induced cold and mechanical allodynia. Moreover, single-prolonged stress induced abnormality in the limbic hypothalamus-pituitary-adrenal axis was reversed by trans-resveratrol, as evidenced by the fact that trans-resveratrol reversed the differential expression of glucocorticoid receptor in the anxiety- and pain-related regions. In addition, trans-resveratrol increased protein kinase A, phosphorylated cAMP response element binding protein, and brain-derived neurotrophic factor levels, which were decreased in mice subjected to single-prolonged stress. Conclusions: These results provide compelling evidence that trans-resveratrol protects neurons against posttraumatic stress disorder-like stress insults through regulation of limbic hypothalamus-pituitary-adrenal axis function and activation of downstream neuroprotective molecules such as protein kinase A, phosphorylated cAMP response element binding protein, and brain-derived neurotrophic factor expression.


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