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Brain-derived neurotrophic factor promotes immune reconstitution following radiation injury via activation of bone marrow mesenchymal stem cells. PLoS One 2021;16(10):e0259042

Date

10/26/2021

Pubmed ID

34695155

Pubmed Central ID

PMC8544859

DOI

10.1371/journal.pone.0259042

Scopus ID

2-s2.0-85117930366   1 Citation

Abstract

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 PDGFRI?+ 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.

Author List

Sharma GP, Frei AC, Narayanan J, Gasperetti T, Veley D, Amjad A, Albano K, Fish BL, Himburg HA

Author

Heather A. Himburg PhD Associate Professor in the Radiation Oncology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Brain-Derived Neurotrophic Factor
Disease Models, Animal
Female
Flavones
Immune Reconstitution
Interleukin-6
Leukemia Inhibitory Factor
Male
Mice
Radiation Injuries
Receptor, trkB
Signal Transduction
Thymus Gland