Effects Of Resveratrol Activating SIRT1/PGC-1 Pathway On Cognitive Function

The part of the limbic system of human body envelops the hippocampus,which is the main area involved in cognitive memory.The short-term memory of human activities requires the participation of the hippocampus.For example,damage to the hippocampus will inevitably affect short-term memory and learning.After traumatic brain injury（TBI）,whether long-term or short-term,most patients will have varying degrees of cognitive impairment,some of which will be complicated with serious degenerative nervous system diseases,such as Alzheimer’s disease（AD）,Parkinson’s disease（PD）,etc.Usually,the injury of TBI is mainly due to the injury of cerebral cortex caused by mechanical collision or intracerebral hemorrhage.Most patients have motor and sensory disorders after TBI.After TBI direct injury,most of them are accompanied by secondary injury.The main reason is that external factors will change the internal environment of the brain,mainly due to inflammatory factors,energy metabolism disorders,oxygen free radicals,stress response,etc.These factors often cause functional changes in other no injured areas.We have known that hippocampal region is related to cognitive function,and synapse plays an important role in cognitive function,but we don’t know the relationship between them very well.Synapse is an important structure involved in signal transmission between neurons.Synapses are mainly composed of presynaptic membrane,synaptic cleft and postsynaptic membrane.The transmission of electrical and chemical signals is based on the integrity of synapses.In the existing studies,synapses are found to be involved in the formation of memory and cognition.Damage to the hippocampus can lead to a decline in memory because memory is formed in the hippocampus.After TBI,we found mild or severe cognitive impairment in many clinical patients,which we believe may be related to synaptic loss in the hippocampus.In the previous work,we found that the content of synaptophysin in the hippocampus on the injured side of mouse hippocampus after TBI decreased compared with the control group,and synaptophysin is an important factor involved in synaptic genesis and remodeling.At present,the research on whether SIRT1 is involved in synaptic formation is still in its infancy,but some articles have found that the change of SIRT1 affects not only the morphology and function of synapses,but also the number of synapses.This discovery provides a possible research factor for synaptic loss found in various neurodegenerative diseases.During the whole experiment,we detected the changes of SIRT1 content in the ipsilateral hippocampus of TBI by Western blot.Compared with sham group（three days after TBI）,we found that the lowest point of SIRT1 appeared near 2 days after TBI.Using resveratrol intervention,it was found that the contents of SIRT1,PGC-1and synaptophysin syn were significantly decreased in the TBI group compared with the placebo group.We also gave SIRT1 inhibitor ex-527.Compared with TBI +resveratrol mice,the contents of SIRT1,PGC-1 and syn decreased in mice given SIRT1 inhibitor ex-527.We also gave SIRT1 agonist srt1720,which had the same result trend as resveratrol.The contents of SIRT1,PGC-1 was higher than TBI group.And synaptophysin syn was also higher than TBI group.In animal behavioral experiments,we tested mice through the Y-maze test.Two days after TBI was selected as the time point.The results showed that,compared with the sham-operated group,the cognitive function of the mice 2 days after TBI was significantly reduced,and the cognitive function of the mice was significantly improved after resveratrol.In the previous research results,we can know that SIRT1 and synaptophysin are expressed in hippocampal region by immunofluorescence technology.Our experimental results show that: 1 After TBI,the content of SIRT1 in the hippocampus of mice decreased and reached the lowest point about two days.2.In TBI mouse model,resveratrol can activate SIRT1 and increase the content of synaptophysin in hippocampus.3.After administration of SIRT1 inhibitor ex-527 on the basis of resveratrol group,the content of synaptophysin decreased compared with resveratrol group.4.TBI mice were given SIRT1 agonist by intraperitoneal injection,and the synaptophysin content in hippocampus was significantly higher than that in TBI group.5.The results of the Y-maze test showed that the cognitive ability of the mice in the resveratrol group was significantly improved compared with the TBI group.In conclusion,these results strongly prove that resveratrol can improve cognitive impairment after TBI through SIRT1 / PGC-1 pathway and has neuroprotective function.It provides a possible treatment for the prevention of cognitive impairment after TBI.