Brain-derived neurotrophic factor promotes immune reconstitution following radiation injury via activation of bone marrow mesenchymal stem cells

Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor family which has been extensively studied for its roles in neural development, long-term memory, brain injury, and neurodegenerative diseases. BDNF signaling through tropomyosin receptor kinase B (TrkB) stimulates neuron...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Guru Prasad Sharma, Anne C. Frei, Jayashree Narayanan, Tracy Gasperetti, Dana Veley, Asma Amjad, Katherine Albano, Brian L. Fish, Heather A. Himburg
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4a3d44adb8f54c72b98d101c8574d44e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4a3d44adb8f54c72b98d101c8574d44e
record_format	dspace
spelling	oai:doaj.org-article:4a3d44adb8f54c72b98d101c8574d44e2021-11-04T06:09:18ZBrain-derived neurotrophic factor promotes immune reconstitution following radiation injury via activation of bone marrow mesenchymal stem cells1932-6203https://doaj.org/article/4a3d44adb8f54c72b98d101c8574d44e2021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544859/?tool=EBIhttps://doaj.org/toc/1932-6203Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor family which has been extensively studied for its roles in neural development, long-term memory, brain injury, and neurodegenerative diseases. BDNF signaling through tropomyosin receptor kinase B (TrkB) stimulates neuronal cell survival. For this reason, small molecule TrkB agonists are under pre-clinical develoment for the treatment of a range of neurodegenerative diseases and injuries. Our laboratory recently reported BDNF is secreted by pro-regenerative endothelial progenitor cells (EPCs) which support hematopoietic reconstitution following total body irradiation (TBI). Here we report BDNF-TrkB signaling plays a novel regenerative role in bone marrow and thymic regeneration following radiation injury. Exogenous administration of BDNF or TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) following myelosuppressive radiation injury promoted faster recovery of mature blood cells and hematopoietic stem cells capable of multi-lineage reconstitution. BDNF promotes hematopoietic regeneration via activation of PDGFRα+ bone marrow mesenchymal stem cells (MSCs) which increase secretion of hematopoietic cytokines interleukin 6 (IL-6) and leukemia inhibitory factor (LIF) in response to TrkB activation. These data suggest pharmacologic activation of the BDNF pathway with either BDNF or 7,8-DHF may be beneficial for treatment of radiation or chemotherapy induced myelosuppression.Guru Prasad SharmaAnne C. FreiJayashree NarayananTracy GasperettiDana VeleyAsma AmjadKatherine AlbanoBrian L. FishHeather A. HimburgPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Guru Prasad Sharma Anne C. Frei Jayashree Narayanan Tracy Gasperetti Dana Veley Asma Amjad Katherine Albano Brian L. Fish Heather A. Himburg Brain-derived neurotrophic factor promotes immune reconstitution following radiation injury via activation of bone marrow mesenchymal stem cells
description	Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor family which has been extensively studied for its roles in neural development, long-term memory, brain injury, and neurodegenerative diseases. BDNF signaling through tropomyosin receptor kinase B (TrkB) stimulates neuronal cell survival. For this reason, small molecule TrkB agonists are under pre-clinical develoment for the treatment of a range of neurodegenerative diseases and injuries. Our laboratory recently reported BDNF is secreted by pro-regenerative endothelial progenitor cells (EPCs) which support hematopoietic reconstitution following total body irradiation (TBI). Here we report BDNF-TrkB signaling plays a novel regenerative role in bone marrow and thymic regeneration following radiation injury. Exogenous administration of BDNF or TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) following myelosuppressive radiation injury promoted faster recovery of mature blood cells and hematopoietic stem cells capable of multi-lineage reconstitution. BDNF promotes hematopoietic regeneration via activation of PDGFRα+ bone marrow mesenchymal stem cells (MSCs) which increase secretion of hematopoietic cytokines interleukin 6 (IL-6) and leukemia inhibitory factor (LIF) in response to TrkB activation. These data suggest pharmacologic activation of the BDNF pathway with either BDNF or 7,8-DHF may be beneficial for treatment of radiation or chemotherapy induced myelosuppression.
format	article
author	Guru Prasad Sharma Anne C. Frei Jayashree Narayanan Tracy Gasperetti Dana Veley Asma Amjad Katherine Albano Brian L. Fish Heather A. Himburg
author_facet	Guru Prasad Sharma Anne C. Frei Jayashree Narayanan Tracy Gasperetti Dana Veley Asma Amjad Katherine Albano Brian L. Fish Heather A. Himburg
author_sort	Guru Prasad Sharma
title	Brain-derived neurotrophic factor promotes immune reconstitution following radiation injury via activation of bone marrow mesenchymal stem cells
title_short	Brain-derived neurotrophic factor promotes immune reconstitution following radiation injury via activation of bone marrow mesenchymal stem cells
title_full	Brain-derived neurotrophic factor promotes immune reconstitution following radiation injury via activation of bone marrow mesenchymal stem cells
title_fullStr	Brain-derived neurotrophic factor promotes immune reconstitution following radiation injury via activation of bone marrow mesenchymal stem cells
title_full_unstemmed	Brain-derived neurotrophic factor promotes immune reconstitution following radiation injury via activation of bone marrow mesenchymal stem cells
title_sort	brain-derived neurotrophic factor promotes immune reconstitution following radiation injury via activation of bone marrow mesenchymal stem cells
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/4a3d44adb8f54c72b98d101c8574d44e
work_keys_str_mv	AT guruprasadsharma brainderivedneurotrophicfactorpromotesimmunereconstitutionfollowingradiationinjuryviaactivationofbonemarrowmesenchymalstemcells AT annecfrei brainderivedneurotrophicfactorpromotesimmunereconstitutionfollowingradiationinjuryviaactivationofbonemarrowmesenchymalstemcells AT jayashreenarayanan brainderivedneurotrophicfactorpromotesimmunereconstitutionfollowingradiationinjuryviaactivationofbonemarrowmesenchymalstemcells AT tracygasperetti brainderivedneurotrophicfactorpromotesimmunereconstitutionfollowingradiationinjuryviaactivationofbonemarrowmesenchymalstemcells AT danaveley brainderivedneurotrophicfactorpromotesimmunereconstitutionfollowingradiationinjuryviaactivationofbonemarrowmesenchymalstemcells AT asmaamjad brainderivedneurotrophicfactorpromotesimmunereconstitutionfollowingradiationinjuryviaactivationofbonemarrowmesenchymalstemcells AT katherinealbano brainderivedneurotrophicfactorpromotesimmunereconstitutionfollowingradiationinjuryviaactivationofbonemarrowmesenchymalstemcells AT brianlfish brainderivedneurotrophicfactorpromotesimmunereconstitutionfollowingradiationinjuryviaactivationofbonemarrowmesenchymalstemcells AT heatherahimburg brainderivedneurotrophicfactorpromotesimmunereconstitutionfollowingradiationinjuryviaactivationofbonemarrowmesenchymalstemcells
_version_	1718445085104799744

Brain-derived neurotrophic factor promotes immune reconstitution following radiation injury via activation of bone marrow mesenchymal stem cells

Ejemplares similares