Charlton Tryston, Prowse Natalie, McFee Ashley, Heiratifar Noora, Fortin Teresa, Paquette Carley, Hayley Shawn
Department of Neuroscience, Carleton University, Ottawa, ON, Canada.
Front Cell Neurosci. 2023 Jun 19;17:1188672. doi: 10.3389/fncel.2023.1188672. eCollection 2023.
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.
小胶质细胞是主要的免疫活性细胞，可保护大脑免受环境应激源的影响，但也可能被驱动释放促炎细胞因子并诱导细胞毒性环境。脑源性神经营养因子（BDNF）对可塑性、突触形成和一般神经元健康的调节很重要。然而，关于BDNF如何影响小胶质细胞活性知之甚少。我们假设BDNF在细菌内毒素的背景下会对原代皮质（出生后第1 - 3天：P1 - 3）小胶质细胞和（胚胎第16天：E16）神经元培养物产生直接调节作用。为此，我们发现脂多糖（LPS）诱导炎症后进行BDNF处理具有显著的抗炎作用，可逆转皮质原代小胶质细胞中白细胞介素-6（IL - 6）和肿瘤坏死因子-α（TNF - α）的释放。这种调节作用可传递至皮质原代神经元，即LPS激活的小胶质细胞培养基添加到单独的神经元培养物中时能够产生炎症效应，同样，BDNF预处理可减弱这种效应。BDNF还逆转了LPS暴露对小胶质细胞的整体细胞毒性影响。我们推测BDNF可直接在调节小胶质细胞状态中发挥作用，从而影响小胶质细胞与神经元的相互作用。
