The effects of extinction training on DNA methylation protein and hippocampal newborn neurons in the conditioned-fear rat model / 中华行为医学与脑科学杂志

ABSTRACT

Objective To investigate the effect of different extinction training on fear memory,DNA methylation protein and hippocampal newborn neurons in adult rats.Methods Male SD rats were randomly divided into four groupsnaive group,conditioned fear group,traditional-extinction group and retrieval-extinction group.Conditioned fear models were established by tone paired foot shock,and retrieval-extinction training or traditional-extinction training were performed in adult rats.Retention test,Western blot and immunnohischemistry were used to detect the no-freezing time percentage,the DNA methylation protein level,the newborn neurons respectively at 1d,4d and 7d after different extinction training.Results The traditional-extinction group((28.06± 11.33) ％) or retrieval-extinction group((30.28± 11.48) ％) had higher percentage of no-freezing time than that of conditioned fear group((21.35±9.45) ％),and lower percentage of no-freezing time than that of naive group ((75.65±8.69)％) (t=2.204,2.517,7.955,7.023,all P＜0.05) at the fourth day after extinction training.At the seventh day after extinotion training,the retrieval-extinction group ((69.72±13.62)％) had higher percentage of no-freezing time than traditional-extinction group((24.27± 11.67)％,t=7.052,P＜0.01) or conditioned fear group((50.64± 12.51)％,t=2.451,P＜0.05),and showed no significant difference compared with naive group((72.03±9.36) ％,t=0.251,P＞0.05).The expressions of Dnmt-1 and MBD-2 in traditional-extinction group or retrieval-extinction group were lower than those in conditioned fear group,and higher than those in naive group (P＜0.05) at 4 d after extinction.training.At 7 d after extinction training,the expressions of Dnmt-1 and MBD-2 in retrieval-extinction group were lower than those in traditional-extinction group or conditioned fear group (P＜0.05),and there was no significant difference between retrieval-extinction group and naive group.The Brdu-positive cells of traditional-extinction group or retrieval-extinction training were higher than conditioned fear group,and less than naive group (P＜0.05) at the fourth day after extinction training.At the seventh day after extinction training,the Brdu-positive cells in retrieval-extinction group were higher than those in traditional-extinction group or conditioned fear group (P＜0.05),and there was no significant difference between retrieval-extinction group and naive group.Conclusion The extinction training can decrease fear memory of rats with conditioned fear memory,and the effect of retrieval-extinction training were better than traditional-extinction training,which may be associated with the increases of hippocampus newborn neurons and the decline of DNA methylation.