Résumé
Objective:To observe any therapeutic effect of repeated transcranial direct current stimulation (tDCS) on rats modeling neuropathic pain and explore possible mechanisms.Methods:Forty adult male Sprague-Dawley rats were randomly divided into a normal group ( n=10), a sham operation group ( n=10), a treatment group ( n=10) and a sham treatment group ( n=10). A model of chronic constriction injury of the sciatic nerve was established in the latter two groups. Fourteen days after the modeling, the treatment group was given tDCS for 8 consecutive days, while the sham treatment group received sham stimulation, and the other 2 groups did not receive any intervention. Von Frey and hotplate tests were used to test the rats′ pain thresholds 1 day before, as well as 14 and 22 days after the surgery (i.e., 8 days after the end of the treatment). Spinal cord tissue samples were taken to detect the protein expressions of N-methyl-D-aspartic acid receptor 2B, gamma-aminobutyric acid receptor types A (GABA a-R) and B (GABA b-R) using western blotting. Results:On the 14th day after the operation the average 50% MWT and WTL values of the sham treatment and treatment groups had decreased significantly compared with the sham operation group. By the 22nd day the average 50% MWT and WTL values of the treatment group were significantly higher than those of the sham treatment group, but there was no significant change in the treatment group′s average WTL between the 21st and 22nd days. On the 22nd day after the operation the average NR2B-NMDA-R level of the sham treatment group were significantly higher than that of the sham operation group, while the average GABA a-R and GABA b-R levels were significantly lower. At the same time point the treatment group′s average NR2B-NMDA-R level had decreased significantly compared to the sham treatment group, while the average GABA a-R level had increased significantly. There was no significant difference in average GABA b-R level between the treatment group and the sham treatment group at that point. On the 22nd day there was also no significant difference in the average NR2B-NMDA-R level between the treatment group and the sham operation group. Conclusions:Repeated tDCS can effectively relieve neuropathic pain. The relief of hyperalgesia is more significant than that of mechanical allodynia. A possible mechanism may be the down-regulation of spinal NR2B-NMDA-R to normal levels and modest up-regulation of GABA a-R.
Résumé
Major depressive disorder (MDD) is a common mood disorder that affects almost 20% of the global population. In addition, much evidence has implicated altered function of the gamma-aminobutyric acid (GABAergic) system in the pathophysiology of depression. Recent research has indicated that GABA receptors (GABARs) are an emerging therapeutic target in the treatment of stress-related disorders such as MDD. However, which cell types with GABARs are involved in this process is unknown. As hippocampal dysfunction is implicated in MDD, we knocked down GABARs in the hippocampus and found that knocking down these receptors in astrocytes, but not in GABAergic or pyramidal neurons, caused a decrease in immobility in the forced swimming test (FST) without affecting other anxiety- and depression-related behaviors. We also generated astrocyte-specific GABAR-knockout mice and found decreased immobility in the FST in these mice. Furthermore, the conditional knockout of GABARs in astrocytes selectively increased the levels of brain-derived neurotrophic factor protein in hippocampal astrocytes, which controlled the decrease in immobility in the FST. Taken together, our findings contribute to the current understanding of which cell types expressing GABARs modulate antidepressant activity in the FST, and they may provide new insights into the pathological mechanisms and potential targets for the treatment of depression.
Résumé
Objective To compare the effects of propofol and ketamine on long-term memory and the expression of brain N-methylgroup-D-aspartate receptor 2B(NMDAR2B) and Gamma-aminobutyric acid receptor 1(GABAR1) in aged rats, and preliminary investigate the relation between the long-term memory and expression of neurotransmitter receptors in different cerebral areas. Methods The aged male rats were randomly divided into control group,propofol group and ketamine group. Morris water maze training was performed in all the rats of three groups for 5 days. On the 6th day, intraperitoneal injection of 50 mg?mL-1 propofol was administrated in propofol group,80 mg?mL-1 ketamine was intraperitoneally injected in ketamine group,and blank control group was given the same dose of saline.Seven days after the administration,space exploration experiment and navigation experiment test were performed to test the impact on the learning and memory ability of rats. After that, the expression levels of GABAR1 and NMDAR2B in temporal lobe and hippocampal CA1 region of the rat brain were detected by immunofluorescence and FISH technique. Results The results of Morris water maze showed there was no significant difference between propofol group (9.49±1.24) s and blank control group (8.82±2.22) s.There was statistically significant difference between ketamine group (12.04±2.67) s and blank control group (P<0.05),with longer latency time and less number of times of passing through target as compared with blank control group.By using immunohistochemistry and FISH technique,the expression of GABAR1 in temporal lobe and hippocampal CA1 region of the rat brain was not significantly different between propofol group and blank control group,but it was significantly up-regulated in ketamine group as compared with blank control group ( P<0.05) . The expression of NMDAR2B in temporal lobe and hippocampal CA1 region of the rat brain was not significantly different between propofol group and blank control group,but it was significantly down-regulated in ketamine group as compared with blank control group (P<0.05). Conclusion Propofol anesthesia alone had no effect on long-term learning and memory,but ketamine anesthesia can result in long-term learning and memory impairment. The mechanism may be related with down-regulation of the expression of NMDAR2B receptor and up-regulation of GABAR1 not only in CA1 region hippocampus,but also in temporal lobe.