Effects of novel small compounds targeting TrkB on neuronal cell survival and depression-like behavior

Fukuda, Mayu; Takatori, Atsushi; Nakamura, Yohko; Suganami, Akiko; Hoshino, Tyuji; Tsutsumi, Yutaka; Nakagawara, Akira

doi:10.1016/j.neuint.2016.04.017

Cited by 13 publications

(8 citation statements)

References 26 publications

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“…some researchers to suggest that mere regulation of any of these effectors leads to rapid and sustained antidepressant responses. Although this idea has turned out to be promising in some rodent studies (Shirayama et al, 2002;Chen et al, 2012;Fukuda et al, 2016;Hasegawa et al, 2019), it essentially ignores how these molecular events are part of activity-dependent synaptic plasticity (Changeux and Danchin, 1976;Thoenen, 1995;Hensch, 2005;Park and Poo, 2013) (see Introduction). Moreover, such molecular perspectives fail to appreciate the temporal distribution of the effects of ketamine on cortical excitation and plasticity as well as the prolonged influence on depressive symptoms (Fig.…”

Section: Examining Rapid Antidepressant Effects Through Encodingmentioning

confidence: 99%

Encoding, Consolidation, and Renormalization in Depression: Synaptic Homeostasis, Plasticity, and Sleep Integrate Rapid Antidepressant Effects

Rantamäki

Kohtala

2020

Pharmacol Rev

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Brain and Mind Doctoral Program (S.K.), the Orion Research Foundation (S.K.), and the Emil Aaltonen foundation (S.K.). T.R. and S.K. are listed as coinventors on a patent application, wherein new tools enabling the development of rapid-acting antidepressants and the efficacy monitors thereof are disclosed based on the basic principles of ENCORE-D. T.R. and S.K. have assigned their patent rights to the University of Helsinki but will share a percentage of any royalties that may be received by the University of Helsinki.

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Section: Examining Rapid Antidepressant Effects Through Encodingmentioning

confidence: 99%

Encoding, Consolidation, and Renormalization in Depression: Synaptic Homeostasis, Plasticity, and Sleep Integrate Rapid Antidepressant Effects

Rantamäki

Kohtala

2020

Pharmacol Rev

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“…Activated AKT mediated anti-anoikis and apoptosis via mitochondrion-driven apoptotic pathway, rendering cancer cells survival, chemoresistance and invasiveness [ 15 ]. Previous studies have shown that the activation of TrkB by BDNF could mediate the anoikis suppression and metastasis by activating PI3K/AKT pathway [ 16 ]. The overexpression of TrkB has been reported in different malignant tumors, such as neuroblastoma, pancreatic cancer, breast cancer, lung cancer, prostate cancer and myeloma [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

TrkB promotes laryngeal cancer metastasis via activation PI3K/AKT pathway

et al. 2017

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ObjectivesThe aim of our study was to investigate the role of TrkB pathway in tumor occurrence and development for in order to provide theoretical basis to laryngeal cancer therapy.Materials and methodsBiological characteristics of the cells were studied by migration tests and colony forming assay. Gene and protein expression analysis was performed by RT-PCR or western blot. in vivo experiments were conducted in syngeneic BALB/c mice.ResultsSignificant changes in protein and gene expression, including higher expression level of TrkB, were found in cells and laryngeal cancer specimens. we demonstrated that TrkB activates AKT via c-Src, leading to increased proliferation. Also, TrkB induced EMT via increased expression of EMT related transcription factors such as Twist-1 and Twist-2.ConclusionOur data indicate TrkB are overexpressed in laryngeal cancer, and TrkB signaling is involved in tumorigenicity of laryngeal cancer. These observations suggest that TrkB is a promising target for future intervention strategies to prevent tumor metastasis, EMT program in laryngeal cancer.What is already known about this subject?• Cancer of the larynx is one of the most common types of head and neck cancer.• The survival rate of advanced laryngeal cancer is only 30 to 40%.• The tropomyosin-related kinase B receptor (TrkB), together with TrkA and TrkC, are neurotrophin receptors regulating the proliferation and differentiation of neuronal cells.What are the new findings?• TrkB are overexpressed in laryngeal cancer.• TrkB signaling is involved in tumorigenicity of laryngeal cancer.• TrkB acts as a key regulator of the PI3K/AKT signal pathway-mediated tumor metastasis.How might these results change the focus of research or clinical practice?• These observations suggest that TrkB is a promising target for future intervention strategies to prevent tumor metastasis, EMT program in laryngeal cancer. Our study provides molecular insight into the tumor metastasis and has important implications in elucidating oncogenic processes.

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“…Synaptic transmission depends on the functional Trk B receptor. The lack of BDNF-TrkB signal due to the inhibitation of TrkB will reduce the antidepressant effect (25), which suggests that the BDNF-Trk B signaling pathway will participate in the antidepressant process. Kozono et al (26) reported that 5-HT4 receptor coupled with Gs protein can promote dendritic formation in hippocampal neurons, and increased expression of BDNF can induce 5-HT4 receptor to play a role by Trk B signal transduction.…”

Section: Discussionmentioning

confidence: 99%

Effects of Vortioxetine on depression model rats and expression of BDNF and Trk B in hippocampus

Sun

et al. 2020

Exp Ther Med

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Effects of Vortioxetine on the expression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (Trk B) in hippocampus of depressive rats were investigated. Forty-five SD rats were randomly divided into three groups: model control, Vortioxetine and normal control group, with 15 rats in each group. The changes of body mass were recorded within 5 weeks, and the open field test, sugar water preference test and Morris water maze test were performed to evaluate the behavior and mental status of the rats. The expression of BDNF and Trk B in rat hippocampus was detected by enzyme-linked immuno sorbent assay. Compared with the model control group, the body mass, horizontal and vertical movement, sugar and water preference rate of the vortioxetine group in the 5th week were significantly higher than those of the model control group (P<0.05), and significantly lower than those of the normal control group (P<0.05). The escape latency of the Vortioxetine group within 4 days was significantly lower than that of model control group (P<0.05), but higher than that of normal control group (P<0.05). The target quadrant residence time of the Vortioxetine group was significantly lower than that of the model control group (P<0.05), but higher than that of the normal control group (P<0.05). Expression of BDNF and Trk B in the Vortioxetine group was significantly higher than that in the model control group (P<0.05), but lower than that of the normal control group (P<0.05). Collectively, Vortioxetine can effectively alleviate the symptoms of autonomous and exploratory behavior, and reduce the decrease of learning and memory in depressive rats. Vortioxetine can increase the expression of BDNF and Trk B in depressive rats and alleviate their depressive behavior.

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Effects of novel small compounds targeting TrkB on neuronal cell survival and depression-like behavior

Cited by 13 publications

References 26 publications

Encoding, Consolidation, and Renormalization in Depression: Synaptic Homeostasis, Plasticity, and Sleep Integrate Rapid Antidepressant Effects

Encoding, Consolidation, and Renormalization in Depression: Synaptic Homeostasis, Plasticity, and Sleep Integrate Rapid Antidepressant Effects

TrkB promotes laryngeal cancer metastasis via activation PI3K/AKT pathway

Effects of Vortioxetine on depression model rats and expression of BDNF and Trk B in hippocampus

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