ABSTRACT
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.
ABSTRACT
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.