BDNF produced by cerebral microglia promotes cortical plasticity and pain hypersensitivity after peripheral nerve injury.

Peripheral nerve injury-induced mechanical allodynia is often accompanied by abnormalities in the higher cortical regions, yet the mechanisms underlying such maladaptive cortical plasticity remain unclear. Here, we show that in male mice, structural and functional changes in the primary somatosensor...

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Autores principales:	Lianyan Huang, Jianhua Jin, Kai Chen, Sikun You, Hongyang Zhang, Alexandra Sideris, Monica Norcini, Esperanza Recio-Pinto, Jing Wang, Wen-Biao Gan, Guang Yang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/5030bc8459b24a71915c2d3913f29852
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spelling	oai:doaj.org-article:5030bc8459b24a71915c2d3913f298522021-12-02T19:54:22ZBDNF produced by cerebral microglia promotes cortical plasticity and pain hypersensitivity after peripheral nerve injury.1544-91731545-788510.1371/journal.pbio.3001337https://doaj.org/article/5030bc8459b24a71915c2d3913f298522021-07-01T00:00:00Zhttps://doi.org/10.1371/journal.pbio.3001337https://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Peripheral nerve injury-induced mechanical allodynia is often accompanied by abnormalities in the higher cortical regions, yet the mechanisms underlying such maladaptive cortical plasticity remain unclear. Here, we show that in male mice, structural and functional changes in the primary somatosensory cortex (S1) caused by peripheral nerve injury require neuron-microglial signaling within the local circuit. Following peripheral nerve injury, microglia in the S1 maintain ramified morphology and normal density but up-regulate the mRNA expression of brain-derived neurotrophic factor (BDNF). Using in vivo two-photon imaging and Cx3cr1CreER;Bdnfflox mice, we show that conditional knockout of BDNF from microglia prevents nerve injury-induced synaptic remodeling and pyramidal neuron hyperactivity in the S1, as well as pain hypersensitivity in mice. Importantly, S1-targeted removal of microglial BDNF largely recapitulates the beneficial effects of systemic BDNF depletion on cortical plasticity and allodynia. Together, these findings reveal a pivotal role of cerebral microglial BDNF in somatosensory cortical plasticity and pain hypersensitivity.Lianyan HuangJianhua JinKai ChenSikun YouHongyang ZhangAlexandra SiderisMonica NorciniEsperanza Recio-PintoJing WangWen-Biao GanGuang YangPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 19, Iss 7, p e3001337 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Lianyan Huang Jianhua Jin Kai Chen Sikun You Hongyang Zhang Alexandra Sideris Monica Norcini Esperanza Recio-Pinto Jing Wang Wen-Biao Gan Guang Yang BDNF produced by cerebral microglia promotes cortical plasticity and pain hypersensitivity after peripheral nerve injury.
description	Peripheral nerve injury-induced mechanical allodynia is often accompanied by abnormalities in the higher cortical regions, yet the mechanisms underlying such maladaptive cortical plasticity remain unclear. Here, we show that in male mice, structural and functional changes in the primary somatosensory cortex (S1) caused by peripheral nerve injury require neuron-microglial signaling within the local circuit. Following peripheral nerve injury, microglia in the S1 maintain ramified morphology and normal density but up-regulate the mRNA expression of brain-derived neurotrophic factor (BDNF). Using in vivo two-photon imaging and Cx3cr1CreER;Bdnfflox mice, we show that conditional knockout of BDNF from microglia prevents nerve injury-induced synaptic remodeling and pyramidal neuron hyperactivity in the S1, as well as pain hypersensitivity in mice. Importantly, S1-targeted removal of microglial BDNF largely recapitulates the beneficial effects of systemic BDNF depletion on cortical plasticity and allodynia. Together, these findings reveal a pivotal role of cerebral microglial BDNF in somatosensory cortical plasticity and pain hypersensitivity.
format	article
author	Lianyan Huang Jianhua Jin Kai Chen Sikun You Hongyang Zhang Alexandra Sideris Monica Norcini Esperanza Recio-Pinto Jing Wang Wen-Biao Gan Guang Yang
author_facet	Lianyan Huang Jianhua Jin Kai Chen Sikun You Hongyang Zhang Alexandra Sideris Monica Norcini Esperanza Recio-Pinto Jing Wang Wen-Biao Gan Guang Yang
author_sort	Lianyan Huang
title	BDNF produced by cerebral microglia promotes cortical plasticity and pain hypersensitivity after peripheral nerve injury.
title_short	BDNF produced by cerebral microglia promotes cortical plasticity and pain hypersensitivity after peripheral nerve injury.
title_full	BDNF produced by cerebral microglia promotes cortical plasticity and pain hypersensitivity after peripheral nerve injury.
title_fullStr	BDNF produced by cerebral microglia promotes cortical plasticity and pain hypersensitivity after peripheral nerve injury.
title_full_unstemmed	BDNF produced by cerebral microglia promotes cortical plasticity and pain hypersensitivity after peripheral nerve injury.
title_sort	bdnf produced by cerebral microglia promotes cortical plasticity and pain hypersensitivity after peripheral nerve injury.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/5030bc8459b24a71915c2d3913f29852
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BDNF produced by cerebral microglia promotes cortical plasticity and pain hypersensitivity after peripheral nerve injury.

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