Abstract：Objective: To explore the effect of neuregulin 1 （Nrg1） knockdown in prefrontal cortex （PFC） on the formation of schizophrenia-like phenotypes in mice and its potential mechanism. Methods: A total of 45 adult male C57BL/6 mice were divided into 3 groups with 15 mice in each group based on open field test, including control group, negative control group, Nrg1-siRNA group. Stereotaxic surgery was performed to inject 2 μL negative control siRNA and Nrg1-siRNA in mice PFC of negative control group and Nrg1-siRNA group, while control group were injected with 2 μL PBS. Nrg1 mRNA and NRG1 protein expression in prefrontal cortex were detected by qRT-PCR and Western blotting. The mice with Nrg1 gene knockdown in PFC were evaluated on the prepulse inhibition, open field test, and elevated plus maze. Western blotting was used to detect the expression of vesicular GABA transporter （VGAT） and vesicular glutamate transporter 1 （VGLUT1）. Results: The expression of Nrg1 mRNA and NRG1 protein in the PFC in Nrg1-siRNA group were significantly decreased compared with control group （P<0.01）. In behavior tests, compared with control group, Nrg1-siRNA group showed lower prepulse inhibition（P<0.05）, higher distance and speed of spontaneous movement（both P<0.01）, and the percentage of times and time to enter the open arm was significantly reduced（both P<0.01）. The ratio of VGLUT1/VGAT expression in Nrg1-siRNA group was significantly increased compared with control group. Conclusion: Nrg1 gene knockdown in mice PFC could lead to significant schizophrenia-like behavior characterized by prepulse inhibition disorder, increased spontaneous movement and anxiety, which may be related to the imbalance between inhibitory and excitatory neurotransmitter transporters.
［Key words］neuregulin 1; schizophrenia; mice; prefrontal cortex; brain stereotactic injection
丛启杰,曾荣森,刘耘溪,等. 大脑前额皮层Nrg1基因敲低对小鼠精神分裂症样行为形成的影响[J]. 江苏大学学报:医学版, 2022, 32(03): 213-218.
CONG Qijie, ZENG Rongsen, LIU Yunxi, et al.. Effects of Nrg1 gene knockdown in prefrontal cortex on formation of schizophrenia-like phenotypes in mice. Journal of Jiangsu University(Medicine Edition), 2022, 32(03): 213-218.
