Protective Effects And It’s Mechanisms Of Gastrodia Elata Blume Extract On Memory Deficiency Induced By Stressors Simulated Aerospace

When astronauts in a narrow space for continuous weightlessness,circadian rhythm disorder,limited movement and communication obstruction,it may induce neuropsychiatric disorders,including cognitive function declines such as reaction,judgment,and decision-making during in-orbit flight.Unsimilar to traditional learning and memory disorders,the cognitive decline caused by extreme environmental stress in space is different from the pathological changes of the disease.It is a functional decline that does not have a clear lesion site and specific target,which is difficult for modern medicine to take effect.Traditional Chinese medicine emphasizes the "overall concept" and "syndrome differentiation and treatment".Based on the process of disease occurrence and development,the concept of "Preventive Treatment of Disease" in traditional Chinese medicine is more in line with the improvement of protective functions of cognitive decline caused by environmental stress in space.Gastrodia elata Blume has been traditionally used to treat dizziness,headache,cerebrovascular diseases,and vascular cognitive dysfunction.Fresh Gastrodia elata Blume is a common application form of Gastrodia elata Blume,Modern pharmacological research shows that fresh Gastrodia elata Blume can improve the learning and memory decline caused by sleep rhythm disorder.This paper will adopt two recognized aerospace stress animal models(simulated weightlessness and chronic restraint stress)and multiple behavioral evaluation methods to study the effect and mechanism of the extract of fresh Gastrodia elata Blume(FG)on learning and memory decline caused by environmental stress in space,providing scientific basis for the development of new safe and effective traditional Chinese medicine products which enhance and protect astronauts’ cognitive.The completed research contents mainly include the following aspects:1.The FG has a good effect on improving cognitive function caused by chronic restraint stress(CRS).The effect of FG on cognitive decline in CRS mice was systematically evaluated by using behavioral detection methods such as object location recognition test(OLRT),novel object recognition test(NORT),Morris water maze(MWM)test and dark avoidance test(DAT).The results showed that FG(0.5 and 1 g/kg)significantly increased the discrimination index of OLRT(P<0.05),and shortened the escape latency in MWM navigation experiment(P<0.05,P<0.01),indicating that FG can improve short-term and long-term spatial learning and memory ability.In addition,FG could significantly increase the discrimination index of NORT(P<0.05),and prolong the error latency of DAT(P<0.01),indicating that FG can improve short-term nonspatial learning and memory ability.Through animal behavioral experiments,it was the first time discovered that FG could improve the spatial and non-spatial learning and memory decline caused by CRS.2.It is the first time to prove that FG could improve cognitive function impairment caused by simulated weightlessness.The effects of FG on cognitive decline in simulated weightlessness mice were evaluated by OLRT,MWM test,step-down test(SDT).The results showed that FG(0.5 and 1 g/kg)could improve the discrimination index of OLRT(P<0.05),increased the ability of mice to explore new location of object;shortened the escape latency of mice during the MWM navigation test and working memory test(P<0.05),and increased the number of times of crossing the platform in the MWM exploration experiment(P<0.05);FG could prolong the residence time of mice in the safe zone in the SDT(P<0.05).It was the first time to prove that FG could improve the cognitive function decline caused by simulated weightlessness,which provides a basis for the use of FG to prevent the cognitive decline caused by aerospace weightlessness.3.Study on the effects of chemical components parishin B(PB)and parishin C(PC)in FG on improving memory decline.In the scopolamine model,PB(2,4 mg/kg)can increase the percentage of spontaneous alternations in the Y-maze test(P<0.05);and PC(2 mg/kg)prolong the error latency in DAT(P<0.05).In the CRS model,PB(8 mg/kg)and PC(2 mg/kg)could improve the CRS-induced decrease in the discrimination index of OLRT(P<0.01,P<0.05).PB(2,4 mg/kg)and PC(2,4,8 mg/kg)can increase the percentage of spontaneous alternation in the Y-maze test(P<0.05,P<0.01),indicating the spatial learning and memory improvement ability of PB and PC.PB(2 mg/kg)and PC(8 mg/kg)could increase the discrimination index of NORT(P<0.05),and PB(8 mg/kg)could prolong the error latency of DAT(P<0.05),indicating the improvement effect of PB and PC on non-spatial learning and memory.In addition,through the detection of neurotransmitters,it was found that PB(2,8 mg/kg)and PC(2,4,8 mg/kg)could reduce the content of Glu(P<0.05,P<0.01,P<0.001),PC(4 mg/kg)could reduce the level of Ach(P<0.05),and PB(2,4 mg/kg)and PC(8 mg/kg)could increase the content of Trp(P<0.001,P<0.01).The above results shown that both PB and PC have a certain improvement effect on the cognitive decline induced by scopolamine and CRS in mice.4.Explained that the mechanism of FG in improving cognitive decline is related to regulate inflammatory response.In the aerospace stress environment,it is easy to cause inflammation in the body.Studies have proved that both CRS and simulated weightlessness could lead to inflammatory responses in animals.Therefore,we used ELISA,Western blotting,LC/MS et al.to study the mechanism of FG on improving cognitive decline caused by CRS and simulated weightlessness.The results showed that FG inhibited the release of pro-inflammatory factors TNF-α,IL-6 and IFN-γ in the hippocampus of mice,promoted the levels of anti-inflammatory factors Arg-1,IL-10 and IL-4,and down regulated the expression levels of　NLRP3 and NFκB;FG could increase the antioxidant capacity by up-regulating the level of Nrf2;activate the PI3K-AKT signaling pathway and inhibit the occurrence of mitochondria and apoptosis;up regulating the expression of synaptic plasticity proteins Tncb,SYP and PSD95;by measuring monoamine,cholinergic and amino acid neurotransmitters,it was found that FG could increase the content of DA,NE and Ach,decrease the content of Glu and 5-HT metabolite 5-HIAA,indicating that FG may modulate neurotransmitter transmission by affecting synaptic plasticity.Nissl staining experiment confirmed that the administration of FG improved the structure of neurons in the hippocampus of the model mice.The above results indicated that FG could play an anti-inflammatory role and increase the body’s antioxidant,thereby inhibiting mitochondrial and cell apoptosis,and then up-regulating synaptic plasticity and affecting the transmission of neurotransmitters.In conclusion,this study found that FG could significantly improve the spatial and non-spatial cognitive decline caused by CRS.The experimental results of simulated weightlessness animal model shown that FG can significantly improve the learning and memory function,which is embodied in the improvement of spatial and non-spatial learning and memory animal behaviors.PB and PC are potential pharmacodynamic material basis of FG for improving learning and memory.The effects of FG on improving cognition maybe related to anti-inflammatory,antioxidant,inhibiting mitochondrial fission and apoptosis,increasing synaptic plasticity,and regulating neurotransmitter levels.This study provides a scientific basis for the application of FG to prevent cognitive decline in environmental stress in space,and provides an effective candidate traditional Chinese medicine for people enhancement of brain function with learning and memory decline caused by aerospace stress environment.