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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.
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Frequency and duration of sensory flicker control transcriptional profiles in 5xFAD mice
Current clinical trials are investigating gamma frequency sensory stimulation as a potential therapeutic strategy for Alzheimer's disease (AD); yet, we lack a comprehensive picture of the effects of this stimulation on multiple aspects of brain function. We previously showed that exposing mice to visual flickering stimulation increased mitogen activated protein kinase and nuclear factor kappa-light-chain-enhancer of activated B cells signaling in the visual cortex (VC) in a manner dependent on the duration and frequency of stimulation. Because these pathways control multiple neuronal and glial functions, here we aimed to define the transcriptional effects of different frequencies and durations of audiovisual flicker (AV flicker) stimulation on multiple brain functions. Within the VC, we found that all stimulation frequencies caused fast activation of a module of immune genes within 0.5 h and slower suppression of synaptic genes after 4 h. In the hippocampus, we found that a 20 Hz AV flicker activated a module of genes associated with mitochondrial function, metabolism, and synaptic translation, while 10 Hz rapidly suppressed a module of genes linked to neurotransmitter activity. Collectively, our data indicate that the frequency and duration of AV flicker stimulation control immune, neuronal, and metabolic genes in multiple regions of the brain affected by AD.
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- Award ID(s):
- 1944053
- PAR ID:
- 10613546
- Publisher / Repository:
- American Institute of Physics
- Date Published:
- Journal Name:
- APL Bioengineering
- Volume:
- 9
- Issue:
- 3
- ISSN:
- 2473-2877
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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