ABSTRACT
Ethanol is one of the most widely used and abused psychoactive substances in the world. Long-term and excessive intake of alcohol can damage the central nervous system and lead to impairment of its function. As an important component of the central nervous system, cerebellum is one of the main target organs damaged by ethanol. Acute and chronic ethanol intake can damage human motor coordination, motor learning and some cognitive functions. Its damage mechanism is generally believed to be caused by the abnormal function of cerebellar cortical neural circuit caused by ethanol intake. Combined with recent studies on the mouse model of long-term ethanol intake, this article reviews the cerebellar neural network mechanism of long-term ethanol intake from various aspects, with a view to providing research and development in behavioral movement, motor coordination, cognitive function, depression, and offers new ideas with the rise of precision medicine for treatment. People are increasingly interested in exploring the mechanism of long-term ethanol intake on the cerebellar neural network. How to improve or block the corresponding mechanism based on the mechanism of action found in existing research is an important proposition in future research.
ABSTRACT
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.