proBDNF expression induces apoptosis and inhibits synaptic regeneration by regulating the RhoA-JNK pathway in an in vitro post-stroke depression model

Abstract Brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of post-stroke depression (PSD). However, the precise function and potential mechanism of proBDNF, the precursor form of BDNF, are unknown. In our study, a PSD-like model was established by treating neur...

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Autores principales:	Bangkun Yang, Lesheng Wang, Ying Nie, Wei Wei, Wenping Xiong
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/e39a7d3889bb461fb3a0d8e91ee986a0
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spelling	oai:doaj.org-article:e39a7d3889bb461fb3a0d8e91ee986a02021-11-14T12:11:28ZproBDNF expression induces apoptosis and inhibits synaptic regeneration by regulating the RhoA-JNK pathway in an in vitro post-stroke depression model10.1038/s41398-021-01667-22158-3188https://doaj.org/article/e39a7d3889bb461fb3a0d8e91ee986a02021-11-01T00:00:00Zhttps://doi.org/10.1038/s41398-021-01667-2https://doaj.org/toc/2158-3188Abstract Brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of post-stroke depression (PSD). However, the precise function and potential mechanism of proBDNF, the precursor form of BDNF, are unknown. In our study, a PSD-like model was established by treating neuronal cells with oxygen-glucose deprivation and corticosterone. We found that the protein proBDNF levels were significantly higher in the cortex and hippocampus in the PSD group than in the control group, suggesting that proBDNF plays a role in the pathophysiology of PSD. Furthermore, we re-established the PSD-like cell model using recombinant p75 neurotrophin receptor (p75NTR) or silencing c-Jun N-terminal kinase (JNK), and found that the PSD-induced upregulation of proBDNF was inhibited by recombinant p75NTR and JNK silencing (siJNK), and increased cellular apoptosis. Moreover, the application of recombinant p75NTR and siJNK in the PSD-like cell model significantly reversed the expression of apoptosis-related and depression-related proteins and decreased cellular apoptosis. Our findings suggest that proBDNF is involved in neural plasticity in PSD in vitro. The RhoA-JNK signaling pathway is activated after proBDNF binds to the p75NTR receptor, followed by the expression of apoptosis-related proteins (PSD95, synaptophysin, and P-cofilin), which contribute to PSD progression. The mechanism might involve the promotion of cellular apoptosis and the inhibition of nerve synapses regeneration by proBDNF.Bangkun YangLesheng WangYing NieWei WeiWenping XiongNature Publishing GrouparticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENTranslational Psychiatry, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Bangkun Yang Lesheng Wang Ying Nie Wei Wei Wenping Xiong proBDNF expression induces apoptosis and inhibits synaptic regeneration by regulating the RhoA-JNK pathway in an in vitro post-stroke depression model
description	Abstract Brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of post-stroke depression (PSD). However, the precise function and potential mechanism of proBDNF, the precursor form of BDNF, are unknown. In our study, a PSD-like model was established by treating neuronal cells with oxygen-glucose deprivation and corticosterone. We found that the protein proBDNF levels were significantly higher in the cortex and hippocampus in the PSD group than in the control group, suggesting that proBDNF plays a role in the pathophysiology of PSD. Furthermore, we re-established the PSD-like cell model using recombinant p75 neurotrophin receptor (p75NTR) or silencing c-Jun N-terminal kinase (JNK), and found that the PSD-induced upregulation of proBDNF was inhibited by recombinant p75NTR and JNK silencing (siJNK), and increased cellular apoptosis. Moreover, the application of recombinant p75NTR and siJNK in the PSD-like cell model significantly reversed the expression of apoptosis-related and depression-related proteins and decreased cellular apoptosis. Our findings suggest that proBDNF is involved in neural plasticity in PSD in vitro. The RhoA-JNK signaling pathway is activated after proBDNF binds to the p75NTR receptor, followed by the expression of apoptosis-related proteins (PSD95, synaptophysin, and P-cofilin), which contribute to PSD progression. The mechanism might involve the promotion of cellular apoptosis and the inhibition of nerve synapses regeneration by proBDNF.
format	article
author	Bangkun Yang Lesheng Wang Ying Nie Wei Wei Wenping Xiong
author_facet	Bangkun Yang Lesheng Wang Ying Nie Wei Wei Wenping Xiong
author_sort	Bangkun Yang
title	proBDNF expression induces apoptosis and inhibits synaptic regeneration by regulating the RhoA-JNK pathway in an in vitro post-stroke depression model
title_short	proBDNF expression induces apoptosis and inhibits synaptic regeneration by regulating the RhoA-JNK pathway in an in vitro post-stroke depression model
title_full	proBDNF expression induces apoptosis and inhibits synaptic regeneration by regulating the RhoA-JNK pathway in an in vitro post-stroke depression model
title_fullStr	proBDNF expression induces apoptosis and inhibits synaptic regeneration by regulating the RhoA-JNK pathway in an in vitro post-stroke depression model
title_full_unstemmed	proBDNF expression induces apoptosis and inhibits synaptic regeneration by regulating the RhoA-JNK pathway in an in vitro post-stroke depression model
title_sort	probdnf expression induces apoptosis and inhibits synaptic regeneration by regulating the rhoa-jnk pathway in an in vitro post-stroke depression model
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/e39a7d3889bb461fb3a0d8e91ee986a0
work_keys_str_mv	AT bangkunyang probdnfexpressioninducesapoptosisandinhibitssynapticregenerationbyregulatingtherhoajnkpathwayinaninvitropoststrokedepressionmodel AT leshengwang probdnfexpressioninducesapoptosisandinhibitssynapticregenerationbyregulatingtherhoajnkpathwayinaninvitropoststrokedepressionmodel AT yingnie probdnfexpressioninducesapoptosisandinhibitssynapticregenerationbyregulatingtherhoajnkpathwayinaninvitropoststrokedepressionmodel AT weiwei probdnfexpressioninducesapoptosisandinhibitssynapticregenerationbyregulatingtherhoajnkpathwayinaninvitropoststrokedepressionmodel AT wenpingxiong probdnfexpressioninducesapoptosisandinhibitssynapticregenerationbyregulatingtherhoajnkpathwayinaninvitropoststrokedepressionmodel
_version_	1718429438440374272

proBDNF expression induces apoptosis and inhibits synaptic regeneration by regulating the RhoA-JNK pathway in an in vitro post-stroke depression model

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