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Objective To investigate effects of N-acetylcysteine (NAC) on changes of the behavior and the monoamine neurotransmitters in prefrontal cortex (PFC), striatum (ST), amygdala (AM) and hippocampus (HIP) in rat model of chronic unpredictable stress (CUS), and to explore the possible mechanisms related to the NAC. Methods Thirty-two male Sprague-Dawle (SD) rats were divided into CUS group, fluoxetine group (FLX), NAC group and control group (n=8 for each group). Rats in CUS group, NAC group and FLX group were all fed alone and received CUS for 6 weeks to establish CUS model. Rats in NAC group and FLX group were given NAC and FLX by daily intragastric administration respectively during the last 3 weeks, while rats in CUS group and control group were given the same volume of solvent. Behavioral assessment including weight measurement, sucrose water consumption test, and opened field test were used for evaluation before and after CUS, and before and after intervention. The concentrations of the monoamine neurotransmitters (NE, DA, 5-HT) in PFC, ST, AM and HIP were measured with Coul array HPLC. Results (1) There were more increases in weight gain, sucrose consumption, and distance of horizontal moving and number of up-right, while the number of feces was less, after intervention in control group, NAC group and FLX group than those of CUS group (P<0.05). (2) Neurotransmitters including NE, DA and 5-HT were significantly decreased in PFC, ST, AM and HIP in CUS group compared with that of control group (P<0.05). The monoamine neurotransmitter (NE, DA and 5-HT) were significantly increased in the brain region (PFC, ST, AM and HIP) in NAC group and FLX group than those of CUS group (P < 0.05). Conclusion NAC and fluoxetine can effectively improve the depressive behavior of the CUS rats, increase the contents of monoamine neurotransmitters including NE, DA and 5-HT in PFC, AM, ST and HIP brain regions.
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Objective To explore the role of histone H3 acetylation modification of brain derived neurotrophic factor (BDNF) in the pathogenesis of Alzheimer's disease (AD).Methods 2 months and 8 months SAMP8 mice were used as AD model.Morris water maze was used to detect the impairment of learning and memory.Western blot was used to detect BDNF protein expression in the hippocampus,and chromatin immunoprecipitation (CHIP) was applied to study the changes of histone H3 acetylation in different BDNF promoters.Results The results of water maze test showed that the time across the target quadrant in 8 months SAMP8 mice(0.9±0.4) was significant declined compared with that of 2 months SAMP8 mice(3.7 ± ±0.9) and 8 months SAMR1 mice (3.3±0.6)(all P＜0.05).Meanwhile,compared with 2 months SAMP8 mice ((23.9±4.0) s) and 8 months SAMR1 mice ((21.5± 2.3) s),target quadrant time in the 8 months SAMP8 mice((11.7±2.8) s) was also significantly reduced(both P＜0.05).The western blot showed the expression of BDNF in the hippocampus of 8 months SAMP8 mice was significantly decreased compared with that of 2 months SAMP8 mice and 8 months SAMR1 mice(P＜0.05).Lastly,CHIP assays showed that histone H3 acetylation of BDNF exon Ⅳ and Ⅵ in the hippocampus of 8 months SAMP8 mice were remarkably decreased(P＜0.05) compared with that of 2 months SAMP8 mice and 8 months SAMR1 mice.There was no significant change of histone H3 acetylation of BDNF exon Ⅰ and Ⅲ among all groups(P＞0.05).Conclusion Histone H3 acetylation of BDNF exon Ⅳ and Ⅵ is reduced during the development of AD,which may be the mechanism underlying the impairment of learning and memory in AD.
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Objective To identify the role of the IKK / NF-kappa B signaling pathways in the acquisition and consolidation of extinction memory in conditioning fear.Methods Aduh SD rats were treated with nuclei buried surgery.After a week recovery from nuclei buried surgery,adult SD rats accepted auditory fear conditioning training.Before the extinction training,bilateral intra-BLA infusion of sulfasalazine(SSZ),an inhibitor of IKK/NFκ B,and Vehicle were done.The freezing time were tested on the 24h and 1w after the extinction.Results After training,all the rats showed higher percentage of freezing time than the baseline(Vehicle:pre-CS 21.16％,post-CS 71.23％,P＜0.01 ; SSZ:pre-CS 22.23％,post-CS 72.14％,P＜0.01).The percentage of freezing time had no significant difference(SSZ 47.52％,Vehicle 46.20％,P＞0.05)between Vehicle and SSZ at the end of extinction training.However,SSZ groups showed significantly higher percentage of freezing time than the control group on the 24h(Vehicle 41.03％,SSZ 60.51％,P＜0.01) and the same was found on 1 weck test(Vehicle 34.17％,SSZ 57.21％,P＜ 0.01).The rats injection with SSZ showed significant fear response for the auditory fear condition.Conclusion All above results suggest that interference of IKK/NF-κ B signaling pathway impaire the consolida tion but have no effect on the acquisition of fear extinction memory in conditioning fear.The available date could provide us some clinical guidance in the treatment of post-traumatic stress disorder and panic disorder.
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ObjectiveTo identify the effects of venlafaxiue on the acquisition and consolidation of fear extinction memory in conditioning fear memory extinction model.MethodsMale Sprague-Dawley rats were treated with fear conditioning training in the A environment.Before the extinction training,all the experimental rats were given different doses of venlafaxine intraperitoneal injection.After 24 hours,all the rats test in the B environment.ResultsRepeated-measures ANOVA were conducted on the percent of freezing time for between-session extinction,test condition (F2,44 =458.958,P＜0.001 ) and VEN dose(F2,22 =43.026,P＜0.001 ) and a Test condition * Treatment interaction (F4,44 =31.363,P ＜ 0.001 ).For the within-session,post hoc comparisons indicated that the three groups that received different dose of VEN (0,20 and 40 mg/kg) did not differ from each other (P ＞ 0.05 ),indicating similar extinction following the post-conditioning.The rats injected with high-dose venlafaxine (40 mg/kg) intraperitoneally before extinction training showed pro,motion of between-subjects extinction of fear memory,but does not affect the within-subjects extinction.There was no significant catabolism in the rats injected with middle-dose (20 mg/kg).ConclusionThe available date indicate that venlafaxine could promote the extinction of fear memory and there is a dose-dependent relationship of venlafaxine in the facilitation of fear memory.Our results could provide some clinical guidance for the treatment of post-traumatic stress disorder and panic disorder.