ABSTRACT
Objective: To study the treating mechanism of α-humulene on the schizophrenic mice. Methods: The schizophrenic models were established by dizocilpine maleate (MK801), then different concentrations of α-humulene were used to treat the mice by intragastric administration. Open-field experiment and PPI test were carried out to evaluate the spontaneous activity and sensorimotor gating function of mice. Moreover, the frontal cortex MDA, NO levels and hippocampal NRG1, ErbB4 protein expression was detected. Results: The spontaneous activity, sensorimotor gating function, MDA, NO, NRG1 and ErbB4 levels were significantly changed in model mice when compared with normal mice (P < 0.01). Compared with model group, different concentrations of α-humulene notably inhibited spontaneous activity, improved PPI value, increased NO and MDA content, down-regulated ErbB4 and NRG1 protein expression (P < 0.05, P < 0.01). Conclusion: The schizophrenia abnormal behavior of mice was improved by α-humulene via down-regulating NRG1/ErbB4 signaling pathway, so as to achieve the purpose of treating schizophrenia.
ABSTRACT
ObjectiveTo analyze the gene expression of neuregulin1 (Nrg1)mRNA and protein in encephalic region and peripheral blood,and to explore the consistency of the expression in central and peripheral in schizophrenia model rat induced by dizocilpine maleate ( MK801 ).Methods30 adult male SD rats were randomly divided into 3 groups ( 10 cases per group):model group injected with MK801 (0.6 mg/kg and 100μl/20 g)on the right rear of ventrolateral compartment,control group 1 ( no treatment) and control group 2 injected with equal volume normal saline.Nrg1 mRNA was measured in peripheral blood and in prefrontal lobe by using semiquantitative RT-PCR in 3 groups,and Nrg1 protein was measured in encephalic region (prefrontal lobe,dentate band and hippocamp) by using immunohistochemistry.ResultsThere was significant difference of the amount of Nrg1 mRNA among 3 groups (for center:F=9.141,P =0.001 ;for peripheral blood F =8.389,P =0.001 ),and it was higher in model group ( center:2.08 ± 0.64; peripheral blood:1.43 ± 0.46) than that in two control groups ( control group1,center:1.17 ± 0.42,peripheral blood:0.78 ± 0.39 ; control group 2,center:1.31 ± 0.44,peripheral blood:0.79 ± 0.37 ),but no statistical significant difference existed between two control groups.There was positive correlation of Nrg1 mRNA between center and periphery.There was significant difference of Nrg1 protein in prefrontal lobe,dentate band and hippocamp among 3 groups ( F value was 7.275,21.50 and 4.619,and P value was 0.003,0.000 and 0.019,respectively),and it was higher in model( 7.71 ± 2.55,11.67 ± 1.83and 10.18 ±2.08,respectively)than that in two control groups( control group 1:4.89 ± 1.06,7.53 ± 1.14 and 7.10 ± 2.52,respectively; control group 2:5.31 ± 1.39,8.10 ± 1.60 and 7.81 ± 2.50),but no statistical significant difference existed between two control groups.ConclusionMK801 can effect on the expression of Nrg1 gene,Nrg1 mRNA and protein increase in MK801 model rat,and the change is synchronous between center and periphery.