Brain rhythms control microglial response and cytokine expression via NF-& kappa;B signaling

• Type of Material: Article
• Authors: Ashley Prichard, Georgia Institute of Technology; Kristie M. Garza, Georgia Institute of Technology; Avni Shridhar, Georgia Institute of Technology; Christopher He, Georgia Institute of Technology; Sara Bitarafan, Georgia Institute of Technology; Alyssa Pybus, Georgia Institute of Technology; Yunmiao Wang, Emory University; Emma Snyder, Georgia Institute of Technology; Matthew C. Goodson, Georgia Institute of Technology; Tina C. Franklin, Georgia Institute of Technology; Dieter Jaeger, Emory University; Levi B. Wood, Georgia Institute of Technology; Annabelle Singer, Emory University
• Language: English
• Date: 2023-08-01
• Publisher: AMER ASSOC ADVANCEMENT SCIENCE
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1126/sciadv.adf5672
• Title of Journal or Parent Work: SCIENCE ADVANCES
• Volume: 9
• Issue: 32
• Start Page: eadf5672
• End Page: eadf5672
• Grant/Funding Information: This work was supported by National Institutes of Health grant R01-NS-109226 (to A.C.S.), National Institutes of Health grant R01-NS-109226-01S1 (to K.M.G.), National Institutes of Health grant R01-NS-111470 (to D.J.), National Institutes of Health grant R01-AG-075820 (to L.B.W.), National Institutes of Health Cell and Tissue Engineering Biotechnology Training Grant (T32-GM008433), The Coins for Alzheimer’s Research Trust Fund (to L.B.W. and A.C.S.), Packard Award in Science and Engineering (to A.C.S.), friends and alumni of Georgia Tech (to A.C.S.), and NSF CAREER 1944053 (to L.B.W.).
• Keywords: GENE-EXPRESSION; NF-KAPPA-B; MAP KINASE; Multidisciplinary Sciences; LIGHT FLICKER; NEURONAL OSCILLATIONS; ACTIVATION; TRANSCRIPTION FACTOR; RECEPTOR; Science & Technology; CELL; COLONY-STIMULATING FACTOR; Science & Technology - Other Topics
• Research Categories: Biology, Neuroscience; Biology, Cell

Abstract

Microglia transform in response to changes in sensory or neural activity, such as sensory deprivation. However, little is known about how specific frequencies of neural activity, or brain rhythms, affect microglia and cytokine signaling. Using visual noninvasive flickering sensory stimulation (flicker) to induce electrical neural activity at 40 hertz, within the gamma band, and 20 hertz, within the beta band, we found that these brain rhythms differentially affect microglial morphology and cytokine expression in healthy animals. Flicker induced expression of certain cytokines independently of microglia, including interleukin-10 and macrophage colony-stimulating factor. We hypothesized that nuclear factor κB (NF-κB) plays a causal role in frequency-specific cytokine and microglial responses because this pathway is activated by synaptic activity and regulates cytokines. After flicker, phospho–NF-κB colabeled with neurons more than microglia. Inhibition of NF-κB signaling down-regulated flicker-induced cytokine expression and attenuated flicker-induced changes in microglial morphology. These results reveal a mechanism through which brain rhythms affect brain function by altering microglial morphology and cytokines via NF-κB.