Abstract
Neonatal hypoxic-ischemic encephalopathy (HIE) is an obstinate disease that troubles neonatologists. At present, cognitive impairment after HIE has received increasing attention. Synaptic plasticity determines the development of cognitive function, so it is urgent to develop new drugs that can improve HIE-induced cognitive impairment. Hypoxia–ischemia (HI)–induced neuroinflammation affects synaptic plasticity. As a SIRT1 agonist, resveratrol has a powerful anti-inflammatory effect, but whether it has an effect on impaired synaptic plasticity in HIE and the potential mechanism remain unclear. In the present study, resveratrol was used to intervene in hypoxic-ischemic brain injury (HIBI) mice, and the effects on hippocampal synaptic plasticity and further mechanisms were explored through performing neurobehavioral, morphological observations, Golgi sliver staining, western blotting, and quantitative real-time polymerase chain reaction experiments. We first found that resveratrol improves HI-induced long-term cognitive and memory deficits, and then we found that resveratrol reduces hippocampal neuronal damage and increases dendritic spine density and the expression of synaptic proteins. Finally, we found that this effect may be exerted by regulating the neuroinflammatory response mediated by the SIRT1/NF-κB axis. This study provides a new theoretical basis for resveratrol to prevent long-term neurological dysfunction following HIBI.
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This study was supported by the National Natural Science Foundation of China (Grant No. 82060290), the Science and Technology Planed Projects of Jiangxi Provincial Health Commission (Grant No. 202110021), the Science and Technology Project of Jiangxi Provincial Administration of traditional Chinese Medicine (Grant No. 2020A0297), and the Research Foundation for the Double Training Program of Jiangxi Province Children’s Hospital (SPBKT2020009).
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Kai Le participated in the whole design of this study; Xin Peng, Jun Wang, Juan Peng, and Hongqun Jiang conducted the experiments; Kai Le and Xin Peng analyzed the data; Kai Le and Xin Peng wrote original draft; Jun Wang and Juan Peng edited and revised the whole manuscript. All authors read and approved the final version of the manuscript.
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Peng, X., Wang, J., Peng, J. et al. Resveratrol Improves Synaptic Plasticity in Hypoxic-Ischemic Brain Injury in Neonatal Mice via Alleviating SIRT1/NF-κB Signaling–Mediated Neuroinflammation. J Mol Neurosci 72, 113–125 (2022). https://doi.org/10.1007/s12031-021-01908-5
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DOI: https://doi.org/10.1007/s12031-021-01908-5