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Abstract
Demyelination is a common pathological feature in a wide range of diseases, characterized by the loss of myelin sheath and myelin-supporting oligodendrocytes. These losses lead to impaired axonal function, increased vulnerability of axons to damage, and result in significant brain atrophy and neuro-axonal degeneration. Multiple pathomolecular processes contribute to neuroinflammation, oligodendrocyte cell death, and progressive neuronal dysfunction. In this study, we use the cuprizone mouse model of demyelination to investigate long-term non-invasive gamma entrainment using sensory stimulation as a potential therapeutic intervention for promoting myelination and reducing neuroinflammation in male mice. Here, we show that multisensory gamma stimulation mitigates demyelination, promotes oligodendrogenesis, preserves functional integrity and synaptic plasticity, attenuates oligodendrocyte ferroptosis-induced cell death, and reduces brain inflammation. Thus, the protective effects of multisensory gamma stimulation on myelin and anti-neuroinflammatory properties support its potential as a therapeutic approach for demyelinating disorders.
Demyelination leads to nerve damage and inflammation. Here, the authors show multisensory gamma stimulation’s potential to mitigate demyelination and neuroinflammation, suggesting that this might be a therapeutic strategy for demyelinating diseases.
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1 Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, Cambridge, USA (GRID:grid.116068.8) (ISNI:0000 0001 2341 2786)
2 Ltd, Biomage, Edinburgh, UK (GRID:grid.116068.8)
3 Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, Cambridge, USA (GRID:grid.116068.8) (ISNI:0000 0001 2341 2786); Harvard Medical School, Boston Children’s Hospital, Division of Newborn Medicine, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X)
4 Cell Signaling Technology, Danvers, USA (GRID:grid.420530.0) (ISNI:0000 0004 0580 0138)
5 Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, Cambridge, USA (GRID:grid.116068.8) (ISNI:0000 0001 2341 2786); Broad Institute of Harvard and MIT, Cambridge, USA (GRID:grid.66859.34) (ISNI:0000 0004 0546 1623)