ABSTRACT
Objective To study the effect of glycine transporter 1 inhibitor M22 on epileptic sei-zures and cognitive dysfunction in epilepsy mice. Methods A total of 110 C57BL/6 mice were randomly divided into Normal control group (CON group,n=10),Model group (Mod group n=20),M22-1 group (n=20),M22-2 group (n=20),M22-3 group (n=20),M22-4 group ( n=20) according to weight. The chronic epileptic model was established by intraperitoneal injection of PTZ(30 mg/kg). The mice in CON group was injected with normal saline(10 mg/kg). The mice in Mod group were intraperitoneally injected with normal saline (10 ml/kg) and were injected with PT2 30 min later. The mice in M22-1 group,M22-2 group,M22-3 group,M22-4 group were intraperitoneally injected with M22 of corresponding dose(10 mg/kg,20 mg/kg,40 mg/kg,80 mg/kg)respectively,lasting for 2 weeks. Epilepsy seizures of mice in each group were recorded. The learning and memory function of epilepsy mice were evaluated by Morris water maze test . Then the mice were sacrificed and the apoptosis related proteins Bcl-2,Bax,Cyt-c in the cerebral cortex of mice were meas-ured by Western blot. Results (1)The mortality kindling rate,epileptic seizure grade and rate of tonic clo-nus in M22-2 and M22-3 group were significantly lower than those in Mod,M22-1 and M22-4 group( all P<0. 05). (2) In the directional navigation experiment,the escape latency of mice in each group decreased with time. On the 4th day,the escape latency of mice in M22-3 group was significantly shorter than that in Mod group,and the difference was statistically significant ((30. 24±9. 46),(16. 05±5. 72),t=20. 36,P<0. 05). In space exploration experiment,compared with Mod group,M22-3 group had more times of crossing platform ((6. 45±3. 62),(3. 23±2. 47),t=38. 63,P=0. 004) and longer time of target quadrant activity((21. 53± 6. 38) s,(11. 52±3. 15) s,t=37. 53,P<0. 05). (3)It was showed by Western blotting that the relative ex-pression levels of Bcl-2 in M22-3 group were significantly higher than those in Mod group(P<0. 05),while the Bax and Cyt-c in M22-3 group were significantly lower than those in Mod group(P<0. 05). There was no significant difference in Bcl-2, Bax and Cyt-c between M22-1 group, M22-4 group and model group ( P>0. 05). Conclusion M22 (40 mg/kg) has significant anti-epileptic effect and can effectively improve the cognitive dysfunction of epileptic mice,which may be related to the inhibition of neuronal apoptosis in mice.[Key words] Epilepsy; Glycine transporter 1 inhibitor; M22; Cognitive function; Pentyle-netetrazole
ABSTRACT
Objective Objective TO investigate the potential association between matrix metalloproteinase-9 (MMP-9) gene polymorphisms and risk of ischemic stroke in Western Guangdong population.Methods This hospitalbased case-control study recruited 251 patients with ischemic stroke and 96 controls.Using Multiplex SNaPshot method was used to detect the genotype of MMP-9 gene rs3787268、rs3918241 and rs3918242 polymorphisms.The association between MMP-9 gene polymorphisms and risk of ischemic stroke was analyzed.Results ① There were significant differences in the genotype distribution of rs3787268 between ischemic stroke group and the controls (P=0.042).In the recessive model,the individual risk of A/A genotype was higher (OR=2.21,P=0.046) than that of the G/G+G/A genotype.② Compared with the controls,the genotype and allele distribution of rs3918242 in the ischemic stroke group were significantly different (P=0.007,P=0.038).In the dominant model,the risk of individuals carrying the T genotype was significantly elevated (OR=2.14,P=0.009) compared with individuals with the C/C genotype.③ The genotype distribution of rs3787268 polymorphisms in the LAA but not in no-LAA subgroup was significantly different from that in the controls (P =0.039).The genotype distribution and allele frequency of rs3918242 polymorphisms in the LAA subgroup were significantly different from that of the control group (P=0.009,P=0.047).There was no significant difference in the genotype distribution and allele frequency between no-LAA subtype and the control group.Conclusions The MMP-9 gene rs3918242 and rs3787268 polymorphisms may be the risk factors of ischemic stroke in Han population in the western part of Guangdong province,China.The MMP-9 gene rs3918242 and rs3787268 polymorphisms may be the risk factors of large-artery atherosclerotic stroke.
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Objective To explore the association of ubiquitin-specific proteases 24 (USP24) gene polymorphisms with susceptibility to sporadic Parkinson's disease (PD) in the Han Guangdong population. Methods From August, 2006 to January, 2014, single nucleotide poly-morphisms (SNPs) of rs12138592 and rs6671533 in the intron region of USP24 were genotyped in 200 patients with sporadic PD and 200 healthy controls using the SNaPshot technique. Results There was significant difference in the allele and genotype frequency of rs12138592 between the patients and the controls (P0.05). Conclusion The SNP of rs12138592 in the intron region of USP24 is associated with the susceptibility to sporadic PD in the Han Guangdong population, and the A allele may contribute a protective roles to PD.