• Dan Lv, Yaping Chen, Mengxin Shen, Xu Liu, Yanhua Zhang, Jiangping Xu, and Chuang Wang.
• Ningbo Key Laboratory of Behavioral Neuroscience, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, China; Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, China; Department of Physiology and Pharmacology, Ningbo University School of Medicine, 818 Fenghua Road, Ningbo, Zhejiang, 315211, China.
• Neuropharmacology. 2018 Dec 1; 143: 317-326.

AbstractPrevious studies have revealed that neuropeptide VGF (non-acronymic) C-terminal peptide TLQP-62 rapidly activates brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor/mammalian target of rapamycin (mTOR) signaling and produces antidepressant-like actions in rodents. In addition, acute TLQP-62 infusion also markedly changes the AMPA receptor GluA1 subunit phosphorylation at Ser 845 (pGluA1 Ser845) in the PFC of mice, indicating that the GluA1 may contributes to the rapid antidepressant-like effects of TLQP-62. However, how to regulate the TrkB-mediated signaling and GluA1 changes in the prefrontal cortex (PFC) by TLQP-62 remains unclear. Herein, acute administration of TLQP-62 into PFC produced rapid-acting antidepressant-like effects in mice. Additionally, we confirmed that TLQP-62 ameliorated the depression-like behaviors induced by chronic social defeat stress (CSDS) in mice. Further investigation demonstrated that this effect of TLQP-62 was mediated by activation of TrkB and mTOR, which proceeded to decrease bicaudal C homolog 1 gene (BICC1) and increase synaptic protein expression, including GluA1 subunit and pGluA1 Ser845. Notably, we further found that beneficial effects of TLQP-62 on depression-like behaviors and TrkB/mTOR/BICC1 signaling, GluA1 phosphorylation and GluA1 activation in the PFC of mice were significantly abolished by TrkB antagonist ANA-12. In conclusion, our findings indicate that TrkB/mTOR/BICC1 signaling, GluA1 phosphorylation and GluA1 activation in the PFC may involve in the rapid-acting antidepressant-like actions of TLQP-62 in mice.Copyright © 2018 Elsevier Ltd. All rights reserved.

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