The Effect Of FGF Anti-neuroinflammation And Its Possible Mechanism

Objectives: Neuroinflammation plays an important role in many mental diseases,such as chronic pain,depression and cognitive disorder.These diseases are prone to comorbid or accompany,resulting in postponing or even getting worse,and increasing patients' suffering and the social burden.Fast Green FCF(FGF),as an food dye,have been widely used in food,medicine and scientific research(as protein staining,patch clamp).It has been reported that FGF could inhibit the aggregation of A? oligomer in cellular experiments,thus antagonize its neurotoxicity,however,the effect of FGF in vivo is not clear,and there is no report on whether it can effective against neuroinflammation.This research used complete freund's adjuvant(CFA)to build chronic pain animal model as peripheral neuroinflammation model,used lipopolysaccharide(LPS)to establish depression and congnitive disorder animal model as central neuroinflammation model,eventually we observed the role of FGF in neuroinflammation and oxidative stress,aiming to illuminate the underlying mechanisms of FGF antagonized peripheral neuroinflammation induced by CFA and central neuroinflammation caused by LPS.Methods: Adult male ICR mice were used,aged 6-8 weeks.we built peripheral neuroinflammation model by intraplantar injection of CFA(50 ul,saline 1:1 attenuation),after CFA injection,different doses of FGF(10mg/kg?30mg/kg?100mg/kg)were intraperitoneal injected for consecutive 9 days.Meanwhile,the thermal and mechanical threshold were detected before CFA injection and on day1,day3,day5,day7,day9 after CFA injection.we constructed central neuroinflammation model by intraperitoneal injection of LPS(1mg/kg),and FGF were intraperitoneal injected for continual 7 days before LPS disposed.Then the new object recognition test,sucrose preference test,forced swimming test and novelty-suppressed feeding test were performed to examine the ability of object recognition and depression-like behaviors after LPS conducted 24 h.After the last behavioral tests were carried out,the animals were sacrificed and the plantar tissue,L4~6 spinal cords or brain tissues were acquired,the biochemical indicators were tested by quantitative real-time polymerase chain reaction,enzyme-linked immunosorbent and western blot methods.Results: These research finds that CFA induced mouse thermal and mechanical hyperalgesia,increasing the level of inflammatory factors(IL-1??IL-6?TNF-?)both in plantar tissue and spinal cord,it also enhance neurotrophic factors(BDNF,NGF)of spinal cord,as well as upregulating the expression of P2X4.While after FGF injected for 9 days,the hyperalgesia of 10mg/kg mice were not improved,30mg/kg and 100mg/kg FGF could distinctly ameliorate hyperalgesia;different doses of FGF could restrain the level of inflammatory factors;10 mg/kg and 30mg/kg FGF have no effect on the expression of P2X4 m RNA,but 100mg/kg FGF remarkably inhibited the expression of P2X4 m RNA.It also finds that LPS caused cognitive disorder and depression,improving the level of inflammatory factors(IL-1??IL-6?TNF-?)and decreasing the level of neurotrophic factors BDNF in hippocampus,FGF pretreatment can significantly suppress the generation of cognitive disorder and depression,and refrain the level of inflammatory factors.Conclusions: The current study lent further support that CFA could induce peripheral neuroinflammation and initiate hyperalgesia,which could be improved by FGF in a dosedependent manner,the mechanism might have an connection with its inhibition on P2X4 expression.This study thus proved that LPS could cause central neuroinflammation,and exert cognitive disorder and depression,which could be ameliorate by FGF.