Brain-derived neurotrophic factor (BDNF) has direct anti-inflammatory effects on microglia

Microglia are the primary immunocompetent cells that protect the brain from environmental stressors, but can also be driven to release pro-inflammatory cytokines and induce a cytotoxic environment. Brain-derived neurotrophic factor (BDNF) is important for the regulation of plasticity, synapse format...

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Main Authors: Tryston Charlton, Natalie Prowse, Ashley McFee, Noora Heiratifar, Teresa Fortin, Carley Paquette, Shawn Hayley
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-06-01
Series:Frontiers in Cellular Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fncel.2023.1188672/full
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author Tryston Charlton
Natalie Prowse
Ashley McFee
Noora Heiratifar
Teresa Fortin
Carley Paquette
Shawn Hayley
author_facet Tryston Charlton
Natalie Prowse
Ashley McFee
Noora Heiratifar
Teresa Fortin
Carley Paquette
Shawn Hayley
author_sort Tryston Charlton
collection DOAJ
description Microglia are the primary immunocompetent cells that protect the brain from environmental stressors, but can also be driven to release pro-inflammatory cytokines and induce a cytotoxic environment. Brain-derived neurotrophic factor (BDNF) is important for the regulation of plasticity, synapse formation, and general neuronal health. Yet, little is known about how BDNF impacts microglial activity. We hypothesized that BDNF would have a direct modulatory effect on primary cortical (Postnatal Day 1-3: P1-3) microglia and (Embryonic Day 16: E16) neuronal cultures in the context of a bacterial endotoxin. To this end, we found that a BDNF treatment following LPS-induced inflammation had a marked anti-inflammatory effect, reversing the release of both IL-6 and TNF-α in cortical primary microglia. This modulatory effect was transferrable to cortical primary neurons, such that LPS-activated microglial media was able produce an inflammatory effect when added to a separate neuronal culture, and again, BDNF priming attenuated this effect. BDNF also reversed the overall cytotoxic impact of LPS exposure in microglia. We speculate that BDNF can directly play a role in regulating microglia state and hence, influence microglia-neuron interactions.
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spelling doaj.art-cd5ae89e84d749c3a92a310f38a5b59b2023-06-19T05:45:48ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-06-011710.3389/fncel.2023.11886721188672Brain-derived neurotrophic factor (BDNF) has direct anti-inflammatory effects on microgliaTryston CharltonNatalie ProwseAshley McFeeNoora HeiratifarTeresa FortinCarley PaquetteShawn HayleyMicroglia are the primary immunocompetent cells that protect the brain from environmental stressors, but can also be driven to release pro-inflammatory cytokines and induce a cytotoxic environment. Brain-derived neurotrophic factor (BDNF) is important for the regulation of plasticity, synapse formation, and general neuronal health. Yet, little is known about how BDNF impacts microglial activity. We hypothesized that BDNF would have a direct modulatory effect on primary cortical (Postnatal Day 1-3: P1-3) microglia and (Embryonic Day 16: E16) neuronal cultures in the context of a bacterial endotoxin. To this end, we found that a BDNF treatment following LPS-induced inflammation had a marked anti-inflammatory effect, reversing the release of both IL-6 and TNF-α in cortical primary microglia. This modulatory effect was transferrable to cortical primary neurons, such that LPS-activated microglial media was able produce an inflammatory effect when added to a separate neuronal culture, and again, BDNF priming attenuated this effect. BDNF also reversed the overall cytotoxic impact of LPS exposure in microglia. We speculate that BDNF can directly play a role in regulating microglia state and hence, influence microglia-neuron interactions.https://www.frontiersin.org/articles/10.3389/fncel.2023.1188672/fullmicrogliaBDNFcytokineprimary cultureneurodegenerationneuroimmune
spellingShingle Tryston Charlton
Natalie Prowse
Ashley McFee
Noora Heiratifar
Teresa Fortin
Carley Paquette
Shawn Hayley
Brain-derived neurotrophic factor (BDNF) has direct anti-inflammatory effects on microglia
Frontiers in Cellular Neuroscience
microglia
BDNF
cytokine
primary culture
neurodegeneration
neuroimmune
title Brain-derived neurotrophic factor (BDNF) has direct anti-inflammatory effects on microglia
title_full Brain-derived neurotrophic factor (BDNF) has direct anti-inflammatory effects on microglia
title_fullStr Brain-derived neurotrophic factor (BDNF) has direct anti-inflammatory effects on microglia
title_full_unstemmed Brain-derived neurotrophic factor (BDNF) has direct anti-inflammatory effects on microglia
title_short Brain-derived neurotrophic factor (BDNF) has direct anti-inflammatory effects on microglia
title_sort brain derived neurotrophic factor bdnf has direct anti inflammatory effects on microglia
topic microglia
BDNF
cytokine
primary culture
neurodegeneration
neuroimmune
url https://www.frontiersin.org/articles/10.3389/fncel.2023.1188672/full
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