[Mongolian medicine three acupoints balance needling improves depressive behavior by regulating p11/tPA/BDNF pathway and miRNA-16 of hippocampus and middle raphe nucleus in depression model rats].

Abstract

OBJECTIVE\nTo observe the effect of Mongolian medicine three-acupoints balance needling on the expression of p11/tPA/BDNF pathway and miRNA-16 in the hippocampus and middle raphe nucleus (MRN) in chronic stress depression model rats, so as to explore its mechanisms underlying improvement of depression.\n\n\nMETHODS\nMale SD rats were randomly divided into blank control, model, medication and Mongolian medicine acupuncture (acupuncture) groups, with 12 rats in each group. The depression model was established by using chronic unpredictable mild stress method. The rats in the medication group received gavage of prozac (2 mg/kg, diluted with normal saline, 1 mg/mL) 1 h after stress stimulation, once per day for 28 days, and those in the acupuncture group received three-acupoints (Heyi, Badagan and Xin) needling, once a day for 28 days. The behavioral changes were detected by using open field test and sugar consumption test before modeling and after the intervention. The immunoactivity of p11 and tPA proteins in the MRN, and their expression levels in both the MRN and hippocampus were detected by using immunofluorescence histochemistry and Western blot, separately, and the expression levels of miRNA-16 and BDNF mRNA in the hippocampus and MRN detected by using real-time quantitative PCR.\n\n\nRESULTS\nAfter modeling, the crossing and rearing scores of open field tests and the relative consumption of sucrose in the model group were apparently lower than those of the blank control group (P<0.05), the expression levels of p11 and tPA in the MRN, and those of p11 and tPA proteins and BDNF mRNA in the MRN and hippocampus were significantly down-regulated (P<0.05), while those of miRNA-16 in the hippocampus and MRN were significantly up-regulated (P<0.05). Compared with the model group, the crossing and rearing scores of open field tests and glucose consumption, as well as the expression levels of p11 and tPA proteins and BDNF mRNA in the hippocampus and MRN were obviously increased in both the medication and acupuncture groups (P<0.05), while the expression of miRNA-16 in hippocampus was markedly down-regulated in both the medication and acupuncture groups (P<0.05). No significant differences were found between the acupuncture and medication groups in all the indexes mentioned above (P>0.05).\n\n\nCONCLUSION\nMongolian medicine three-acupoints balance needling can improve the depressive state in depression rats, which may be associated with its effects in up-regulating the expression of p11 and tPA proteins and BDNF mRNA in the hippocampus and MRN and in down-regulating miRNA-16 in the hippocampus, suggesting an involvement of miRNA-16 controlled p11/tPA/BDNF signaling pathway in the antidepressant effect of acupuncture.