Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346290/ https://www.ncbi.nlm.nih.gov/pubmed/34292944 http://dx.doi.org/10.1371/journal.pbio.3001337 |
_version_ | 1783734834886082560 |
---|---|
author | Huang, Lianyan Jin, Jianhua Chen, Kai You, Sikun Zhang, Hongyang Sideris, Alexandra Norcini, Monica Recio-Pinto, Esperanza Wang, Jing Gan, Wen-Biao Yang, Guang |
author_facet | Huang, Lianyan Jin, Jianhua Chen, Kai You, Sikun Zhang, Hongyang Sideris, Alexandra Norcini, Monica Recio-Pinto, Esperanza Wang, Jing Gan, Wen-Biao Yang, Guang |
author_sort | Huang, Lianyan |
collection | PubMed |
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 Cx3cr1(CreER);Bdnf(flox) 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 | Online Article Text |
id | pubmed-8346290 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-83462902021-08-07 BDNF produced by cerebral microglia promotes cortical plasticity and pain hypersensitivity after peripheral nerve injury Huang, Lianyan Jin, Jianhua Chen, Kai You, Sikun Zhang, Hongyang Sideris, Alexandra Norcini, Monica Recio-Pinto, Esperanza Wang, Jing Gan, Wen-Biao Yang, Guang PLoS Biol Research Article 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 Cx3cr1(CreER);Bdnf(flox) 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. Public Library of Science 2021-07-22 /pmc/articles/PMC8346290/ /pubmed/34292944 http://dx.doi.org/10.1371/journal.pbio.3001337 Text en © 2021 Huang et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Huang, Lianyan Jin, Jianhua Chen, Kai You, Sikun Zhang, Hongyang Sideris, Alexandra Norcini, Monica Recio-Pinto, Esperanza Wang, Jing Gan, Wen-Biao Yang, Guang BDNF produced by cerebral microglia promotes cortical plasticity and pain hypersensitivity after peripheral nerve injury |
title | 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_short | 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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346290/ https://www.ncbi.nlm.nih.gov/pubmed/34292944 http://dx.doi.org/10.1371/journal.pbio.3001337 |
work_keys_str_mv | AT huanglianyan bdnfproducedbycerebralmicrogliapromotescorticalplasticityandpainhypersensitivityafterperipheralnerveinjury AT jinjianhua bdnfproducedbycerebralmicrogliapromotescorticalplasticityandpainhypersensitivityafterperipheralnerveinjury AT chenkai bdnfproducedbycerebralmicrogliapromotescorticalplasticityandpainhypersensitivityafterperipheralnerveinjury AT yousikun bdnfproducedbycerebralmicrogliapromotescorticalplasticityandpainhypersensitivityafterperipheralnerveinjury AT zhanghongyang bdnfproducedbycerebralmicrogliapromotescorticalplasticityandpainhypersensitivityafterperipheralnerveinjury AT siderisalexandra bdnfproducedbycerebralmicrogliapromotescorticalplasticityandpainhypersensitivityafterperipheralnerveinjury AT norcinimonica bdnfproducedbycerebralmicrogliapromotescorticalplasticityandpainhypersensitivityafterperipheralnerveinjury AT reciopintoesperanza bdnfproducedbycerebralmicrogliapromotescorticalplasticityandpainhypersensitivityafterperipheralnerveinjury AT wangjing bdnfproducedbycerebralmicrogliapromotescorticalplasticityandpainhypersensitivityafterperipheralnerveinjury AT ganwenbiao bdnfproducedbycerebralmicrogliapromotescorticalplasticityandpainhypersensitivityafterperipheralnerveinjury AT yangguang bdnfproducedbycerebralmicrogliapromotescorticalplasticityandpainhypersensitivityafterperipheralnerveinjury |