Natural Borneol Attenuates Behavioral Deficits By Modulating Glutamate And Its Transporters Expression Level In MPTP Parkinson’s Disease Model Mice

Objective: Exploring the ameliorative effects of natural borneol on behavioral deficits and potential mechanisms in MPTP Parkinson’s disease model mice.Methods: The model of PD mice was established by intraperitoneal injection of MPTP solution.The mice were randomly divided into five groups: control group,MPTP group(20 mg/kg),(+)-borneol(7.5 mg/kg)+ MPTP,(+)-borneol(15 mg/kg)+ MPTP and(+)-borneol(30 mg/kg)+ MPTP.The behavior of mice was studied by the balance beam test,the new object recognition test,and the elevated plus maze test.The extracellular fluid of the mouse striatum was measured online by brain microdialysis sampling combined with UPLC-MS/MS technique to determine the levels of Glu,Gln,GABA,and Gly.Examination of glutamate release from the striatum of mice by depolarizing stimulation produced by KCl and NMDA solutions.The expression levels of glutamate transporter and receptor proteins as well as m RNA in the mouse striatum were measured by Western blot and RT-q PCR experiments.Results: Compared with the control group,the time to cross the balance beam was significantly increased and OE%,OT% and DI were significantly decreased in the model group;compared with the model group,the time to cross the balance beam was shortened and OE% and OT% and DI were significantly increased in the low,medium and high dose natural borneol groups.Compared with the control group,the levels of Glu,Gln,GABA and EI in the striatum of mice of the model group were increased;compared with the model group,the levels of Glu,Gln,GABA and EI in the medium and high doses of natural borneol group were significantly decreased,and the levels of Gly in the striatum of mice of each group was not significantly different.Compared with the control group,the release of Glu was significantly reduced in the model group by NMDA and KCl,and there was no significant difference in the release of Glu induced by NMDA and KCl in the low,medium and high doses of natural borneol compared with the model group.Compared with the model group,the expression of EAAT1,EAAT2 and VGLUT2 protein and m RNA in the striatum of mice with medium to high dose of natural borneol was significantly increased,while the expression of NR2 B was significantly decreased,and there was no significant difference in the expression of VGLUT1 protein and m RNA.Conclusion: The mice in the model group showed motor and cognitive dysfunction and anxiety symptoms,indicating successful modeling.Low,medium and high doses of natural borneol significantly improved the motor and cognitive dysfunction and anxiety symptoms in mice,suggesting that natural borneol may have improved the behavioral deficits of MPTP-induced mice through the glutamatergic pathway.Although natural borneol did not modulate NMDA and KCl-induced glutamate release,prevented the MPTP-induced increase of glutamate level and EI in the extracellular fluid of mouse striatum and inhibited the MPTP-induced alteration of glutamate transporter expression in the mouse striatum,suggesting that natural borneol can improve the behavioral deficits of PD mice by regulating glutamate levels and expression of glutamate transporters.