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Histone lysine methyltransferase( EZH) 1's effect on social and motivational behavioral disordersinduced by schizophrenia
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Abstract:
Objectives This study focused on the effect of histone lysine methyltransferase( EZH) 1 on schizophrenia and its associated behavioral disorders. Methods Seventy C57BL/6 mice were choosen to the following four experiments.( 1)Expressions of EZH1 and EZH2 in brain regions and organs of mice were regions and organs except the cerebellum.( 2)After acute injection of quinpirole, the expression of EZH1 in PFC significantly increased( P< 0.05), while the expressions of EZH2, KDM6A, KDM6B and UTY did not significantly change( P> 0.05).( 3)Compared with mice injected with saline, the expression of EZH1 in PFC of mice injected with clozapine and haloperidol significantly decreased( P < 0.05), while the expression of EZH2 did not significantly changed( P > 0.05).( 4)In the social ability test, EZH1 knockdown increased the time for mice to spend in new cages and to sniff strange mice( P<0.05). In the forced swimming test, EZH1 knockdown reduced the immobility time of the mice and increased the swimming time in mice( P < 0.05). Conclusions EZH1 is highly expressed in various brain regions of mice, especially in PFC of quinpiroleinduced schizophrenia mice. EZH1 is extremely sensitive to antipsychotic drugs, and its knockdown increases the social ability and reduces behavioral despair of mice. detected by real-time quantitative polymerase chain reaction( PCR) and Western Blot.( 2)Mice were given an intraperitoneal injection with 3 mg/kg quinpirole hydrochloride to establish an animal model of schizophrenia, and the control group was given an equal volume of physiological saline. The expressions of histone modificationrelated proteins in the prefrontal cortex( PFC) of mice were measured at 10 min after administration(. 3)Mice were given intraperitoneal injection with 5 mg/kg of clozapine or 0.5 mg/kg of haloperidol, and the control group was injected with an equal volume of physiological saline. The expressions of EZH1 and EZH2 in PFC was measured at 21 days after injection.( 4)AAV-m-EZH1-shRNA was injected into the medial PFC of the mice to knock down EZH1, and the control group was injected with interfering shRNA. The behaviors of the mice were measured at 2 weeks after injection. Results (1)EZH1 is highly expressed in the brain regions including the prefrontal cortex, hippocampus, cerebral cortex, subcortical, cerebellum and brainstem, but is low expressed organs including the heart, kidney, liver, lung, stomach and intestines. EZH2 was low expressed in various brain

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