Hippocampal VGF, BDNF And MAPK Involved In Experimental Gulf War Syndrome In Rats

Objective: Gulf War syndrome (GWS) is a serious condition that affects175,000to210,000of the700,000U.S. veterans served in the1990-1991Gulf War. Thiscomplex of multiple concurrent symptoms typically includes cognitive difficulties,persistent headaches, widespread pain, chronic diarrhea, skin rashes and other chronicabnormalities not explained by all-established diagnoses.2000Steele and the definitionof GWS:6groups of symptoms (fatigue/sleep problems, pain, neurological/cognitive/ood symptoms, gastrointestinal symptoms, respiratory symptoms, skin symptoms) atleast three groups, and to rule out to diagnose medical or psychological reasons.2008,the United States formally recognized GWS as a statutory disease. The present studysuggests that Gulf War syndrome, mainly during the war GWV often used against nervegas pyridostigmine (PB) and deal with the sand flies and other noxious pests, pesticides(DEET) and other chemicals. Using magnetic resonance spectral analysis, PETCT andother emerging technologies found in GWS patients with hippocampal, cingulate gyrus,temporal lobe, hypothalamus and other brain regions reduce the size, metabolicdisorders, compromised function. Therefore, consider the GWS is due to chronic stressand long-term contact of small doses of chemical agents to cause the damage of thehippocampus, hypothalamus and other brain regions, and thus a variety of clinicalsymptoms. The purpose of this experiment: Combining the results of previous studies ofthis group, through the establishment of Gulf War syndrome rat model to observe theVGF, the BDNF and the MAPK/Erk’s changes of expression in the rat hippocampus,explore the neurotrophic factor of BDNF, neuropeptide VGF and MAPK/Erk signalingpathway abnormalities associated with Gulf War Syndrome in rat hippocampus damage,whether the pathogenesis of Gulf War syndrome in rats. Methods:36SD rats were randomly divided into control group, restrain-stressgroup and GWS model group. The rats in GWS group were daily given the bromidepyridostigmine (1.3mg/kg/d) soluble in2ml water gavage, subcutaneous injection ofDEET (40mg/kg/d) dissolved in1ml of70%ethanol, and fixed the shackles of20minutes. The rats in restrain-stress group were daily given the2ml pour service,subcutaneous injection of1ml of70%ethanol, fixed irreducible20minutes. The rats incontrol group were only received daily the2ml pour service, subcutaneous injection of1ml of70%ethanol, fixed bound. During the experiment of28days, the body weightsof rats were measured at0days,7days,14days,21days and28days. After the end ofthe experiment, the rats were anesthetized with the sufficient amount of10%chloralhydrate and perfused with4%paraformaldehyde solution. And then the brains wereremoved and hippocampus separated. In half of each group, the rat hippocampus wasprepared by the conventional paraffin sections, using SABC method forimmunohistochemical staining and the VGF/MAPK immunofluorescence doublestaining to observe the rat hippocampus the VGF and BDNF, the MAPK of expression;half isolated from rats hippocampus by western blot quantitative analysis of the VGFand BDNF, the MAPK and other indicators.Results:â'ˆBody weight changes: The body weight at the beginning of theexperiment (day0) and determination of weight for the control of body weight (100%)to calculate the growth rate of all the body weight of rats in each observation time point,using single-factor analysis of variance (one-way ANOVA) found significantdifferences (P <0.01); The body weight growth rates in GWS model rats weresignificantly lower than the control group (P <0.01) and the restrain-stress group (P<0.05).â'‰Immunohistochemistry results: immunohistochemical staining, theobservations in rat hippocampal CA1region of the VGF and BDNF, MAPK expression,restrain-stress group compared with the control group, the GWS model group andcontrol group compared with the GWS model group compared with the restricted stressgroup, the VGF and BDNF, MAPK average optical density decreased, were statisticallysignificant (P <0.05).â'Šimmunofluorescence results: the line by doubleimmunofluorescence staining, observation of hippocampal CA3region of the MAPK,the VGF fluorescence expression changes in the CA1region of immunohistochemicalresults are consistent; the MAPK and VGF expression trends are consistent.â'‹Westernblot analysis: restrain-stress group compared with the control group, the GWS modelwith the control group compared with model group and restrain-stress group compared with the VGF and BDNF, MAPK integral optical density values lower, with statisticalsignificance (P﹤0.05).Conclusion:â'ˆThe body weight gains were reduced in GWS model rats;â'‰Thehippocampal damage was correlated with reduced expression of the neurotrophic factorBDNF in GWS model rats;â'ŠThe hippocampal damage was correlated with reducedexpression of MAPK in GWS model rats;â'‹The down-regulation of hippocampalexpression of neuropeptide VGF in GWS model rats involved in pathegenesis of GulfWar syndrome via the MAPK/Erk signal pathway.