Objective:To investigate the effect of long-term chronic ethanol consumption on the spontaneous discharge activity of Purkinje cells in the cerebellar cortex of mice.Methods:Fifty 3-week-old ICR mice, regardless of gender, were divided into control group and ethanol group according to the random number table method, with 25 mice in each group. The mice in ethanol group were administered 20% ethanol (1.6 g/kg, once a day) by gavage, and the control group mice were given the same volume of 0.9% sodium chloride solution by gavage, and the gavage cycle was 28 days.The electrical activity of cerebellar Purkinje cells induced by sensory stimulation was recorded by patch clamp amplifier and data acquisition software. Statistical analysis was conducted by Clampfit 10.3 software and SPSS 22.0 software, t-test and one-way ANOVA were used to compare the data between the two groups and the data before and after intervention of each group. Results:The electrophysiological results showed that the spontaneous simple spike discharge frequency of Purkinje cells in the cerebellar cortex of mice in ethanol group was lower than that of the control group ((26.8±2.5)%, (34.6±4.7)%; t=26.08, P<0.05), and the coefficient of variation was higher than that of the control group ((27.3±3.3)%, (19.2±2.3)%; t=22.95, P<0.05). After cerebral surface perfusion of GABAA receptor antagonist, the frequency of simple peak potentials in the cerebellar cortex of ethanol mice was higher than before administration ( t=10.19, P<0.05), and the coefficient of variation was lower than before administration ( t=28.36, P<0.05). After brain surface perfusion of GABAA receptor antagonist, there was no significant change in the spontaneous simple peak discharge frequency of cerebellar Purkinje cells in the control group( P>0.05), and the coefficient of variation decreased compared to before administration ( t=6.95, P<0.05). After administering AMPA receptor antagonists on the surface of the brain, there were no significant changes in the discharge frequency and coefficient of variation in both the ethanol group and control group compared to before administration (both P>0.05). After simultaneously blocking AMPA and GABAA receptors, it was found that the spontaneous discharge frequency in ethanol group increased after administration compared to before administration((107.3±4.3)%, (99.7±3.7)%, P<0.05), and the increased value of frequency in the ethanol group was also higher than that of control group ( P<0.05). After simultaneously blocking AMPA and GABAA receptors, the coefficient of variation of the alcohol group and the control group mice were both lower than those before administration (both P<0.05), and the decrease in the alcohol group was higher than that in the control group ( P<0.05). Conclusion:Chronic ethanol exposure significantly inhibited the spontaneous discharge of Purkinje cells in the cerebellum, and the enhancement of inhibitory components was achieved by the inhibitory input mediated by GABAA receptors.

Objective:To investigate the effect of chronic ethanol consumption on sensory information transmission in the cerebellar molecular layer and reveal the mechanism of chronic alcoholism on sensory information transmission and integration in the cerebellar cortex.Methods:Fifty healthy male ICR mice aged 6-8 weeks were randomly divided into saline group(control group)and ethanol consumption group(alcohol group) according to the random number table, with 25 mice in each group.The mice in alcohol group were injected intraperitoneally with 20% ethanol daily, while the mice in control group were injected with the same dose of normal saline. All mice were injected intraperitoneally once a day for 28 days.Through electrophysiological technology, patch-clamp amplifier and data acquisition software were used to record the changes in cerebellar molecular layer field potential of mice in the alcohol group and control group induced by sensory stimulation.Clampfit 10.3 software was used to record and analyze the electrophysiological data. SPSS 22.0 software was used for statistical analysis. Paired t-test and one-way ANOVA were used to analyze the differences before and after treatment. Results:After giving the stimulation of wind blowing, the amplitude of P1 in alcohol group was significantly higher than that in control group ((121.31±3.5)%, (97.2±2.7)%; t=26.08, P<0.05), and the area under the P1 curve (AUC) of the alcohol group was significantly lower than that of the control group ((127.1±4.2)%, (102.2±3.5)%; t=22.95, P<0.05). There was no significant difference in N1 amplitude between the two groups (P>0.05). When L-NNA, an inhibitor of nitric oxide synthase, was perfused into the brain surface of mice, the amplitude of P1 in alcohol group was significantly lower than that before administration ((76.2±4.8)%, (103.5±3.6)%; t=22.60, P<0.05), but there was no difference of the amplitude of P1 before administration and after elution ((101.5±4.6)%) ( t=1.70, P>0.05). After the L-NNA was perfused, the AUC of P1 was significantly lower than that before administration((72.4±5.6)%, (102.7±2.66)% ( t=24. 58, P<0.05), and there was no significant difference between before administration and after elution( (100.6±3.5)%, t=1.81, P>0.05). When L-NNA was perfused into the brain surface of mice, the amplitude of P1 in control group was (104.3±1.6)% and it had no differences compared with before administration(102.2±5.6)%, t=1.84, P>0.05) and after elution(102.5±4.5)%, t=1.92, P>0.05). And the AUC of P1 in control group after perfused L-NNA had no differences compared with before administration(103.5±2.6)%, (102.5±4.6)%) and after elution((101.9±3.7)%, t=0.99, 1.81, both P>0.05). When the mouse brain surface was perfused with NO donor SNAP, the amplitude of P1 in the control group was significantly higher than that before administration( (128.2±3.4)%, (103.5±2.6)%; t=28.89, P<0. 05) and there was no difference between before administration and after elution( (105.4±4.2)% , t=1.93, P>0.05). The AUC of P1((125.4±4.4)%) was higher than before administration((104.3±4.6)% , t=16.60, P<0.05) and there was no difference between before administration and after elution(103.5±4.2)%, t=0.65, P>0.05). Conclusion:Chronic ethanol consumption significantly enhances the inhibitory response, and the enhancement of inhibitory components stems from the activation of the NO signaling pathway.

帕金森氏病(PD)是一种慢性神经系统退行性疾病,目前研究表明肠道菌群紊乱与PD发病之间存在密切联系,本文主要阐述肠道菌群对PD的可能作用机制,以肠道菌群为靶点治疗的研究进展.