PMID- 30284466 OWN - NLM STAT- Publisher LR - 20240227 IS - 1793-6853 (Electronic) IS - 0192-415X (Linking) DP - 2018 Oct 4 TI - Activity Dependent Mammalian Target of Rapamycin Pathway and Brain Derived Neurotrophic Factor Release Is Required for the Rapid Antidepressant Effects of Puerarin. PG - 1-16 LID - 10.1142/S0192415X18500787 [doi] AB - Puerarin is a traditional Chinese medicine with beneficial effects of reduced depression-like behaviors in mice with stress. Previous studies also show that puerarin can produce neuroprotective effect via activating the Akt or increased brain-derived neurotrophic factor (BDNF) expression. Interestingly, BDNF and Akt downstream target, mammalian target of rapamycin (mTOR) mediate the fast-acting antidepressant properties of ketamine. Until now, the involvement of the mTOR signaling pathway or BDNF on puerarin-induced antidepressant effect remains unknown. We aimed to investigate whether the antidepressant-like effect induced by puerarin would associate mTOR signaling pathway and BDNF release. The antidepressant-like effects of puerarin were evaluated using the forced swim test. The activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionaic acid receptor (AMPAR)-mTOR signaling pathway and release of BDNF in the prefrontal cortex were determined. We also investigated the effect of puerarin on AMPAR trafficking through measuring the PKA phosphorylation of AMPAR subunit GluR1. Our present results show that puerarin exerted antidepressant-like responses that was mediated by AMPAR-induced mTOR signaling pathway and associated with increased BDNF release. Moreover, a significant increase in the GluR1 phosphorylation at its PKA site was noted following puerarin treatment. Our findings are the first to demonstrate that the antidepressant-like actions of puerarin require AMPAR-mTOR signaling pathway activation, are associated with an increased BDNF level and facilitate AMPAR membrane insertion. These findings provide preclinical evidence that puerarin may possess antidepressant property which is mediated by the glutamatergic system. FAU - Huang, Chih-Chia AU - Huang CC AD - * Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan. AD - dagger Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan. AD - double dagger Department of Psychiatry, China Medical University, Taichung, Taiwan. FAU - Tsai, Mang-Hung AU - Tsai MH AD - section sign Department of Anatomy, China Medical University, Taichung, Taiwan. FAU - Wu, Ya-Chieh AU - Wu YC AD - ** Department of Nursing, Ching-Kuo Institute of Management and Health, Keelung, Taiwan. FAU - Chen, Kuang-Ti AU - Chen KT AD - dagger Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan. FAU - Chuang, Han-Wen AU - Chuang HW AD - dagger Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan. FAU - Chen, Yun AU - Chen Y AD - paragraph sign Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan. FAU - Tseng, Guan-Woei AU - Tseng GW AD - parallel Department of Medicine, China Medical University, Taichung, Taiwan. FAU - Fu, Pin-I AU - Fu PI AD - parallel Department of Medicine, China Medical University, Taichung, Taiwan. FAU - Wei, I-Hua AU - Wei IH AD - section sign Department of Anatomy, China Medical University, Taichung, Taiwan. LA - eng PT - Journal Article DEP - 20181004 PL - Singapore TA - Am J Chin Med JT - The American journal of Chinese medicine JID - 7901431 OTO - NOTNLM OT - AMPAR OT - Antidepressant-Like OT - BDNF OT - Prefrontal Cortex OT - Puerarin OT - mTOR EDAT- 2018/10/05 06:00 MHDA- 2018/10/05 06:00 CRDT- 2018/10/05 06:00 PHST- 2018/10/05 06:00 [entrez] PHST- 2018/10/05 06:00 [pubmed] PHST- 2018/10/05 06:00 [medline] AID - 10.1142/S0192415X18500787 [doi] PST - aheadofprint SO - Am J Chin Med. 2018 Oct 4:1-16. doi: 10.1142/S0192415X18500787.