Background: Radiation-induced brain injury (RIBI) is a common and severe complication during radiotherapy for head and neck tumor. Repetitive transcranial magnetic stimulation (rTMS) is a novel and non-invasive method of brain stimulation, which has been applied in various neurological diseases. rTMS has been proved to be effective for treatment of RIBI, while its mechanisms have not been well understood.
Methods: RIBI mouse model was established by cranial irradiation, K252a was daily injected intraperitoneally to block BDNF pathway. Immunofluorescence staining, immunohistochemistry and western blotting were performed to examine the microglial pyroptosis and hippocampal neurogenesis. Behavioral tests were used to assess the cognitive function and emotionality of mice. Golgi staining was applied to observe the structure of dendritic spine in hippocampus.
Results: rTMS significantly promoted hippocampal neurogenesis and mitigated neuroinflammation, with ameliorating pyroptosis in microglia, as well as downregulation of the protein expression level of NLRP3 inflammasome and key pyroptosis factor Gasdermin D (GSDMD). BDNF signaling pathway might be involved in it. After blocking BDNF pathway by K252a, a specific BDNF pathway inhibitor, the neuroprotective effect of rTMS was markedly reversed. Evaluated by behavioral tests, the cognitive dysfunction and anxiety-like behavior were found aggravated with the comparison of mice in rTMS intervention group. Moreover, the level of hippocampal neurogenesis was found to be attenuated, the pyroptosis of microglia as well as the levels of GSDMD, NLRP3 inflammasome and IL-1β were upregulated.
Conclusion: Our study indicated that rTMS notably ameliorated RIBI-induced cognitive disorders, by mitigating pyroptosis in microglia and promoting hippocampal neurogenesis via mediating BDNF pathway.
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http://dx.doi.org/10.1186/s12964-024-01591-0 | DOI Listing |
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Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
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Complex Carbohydrate Research Center, University of Georgia, Athens, GA, USA. Electronic address:
Global healthcare systems are under tremendous strain due to the increasing prevalence of neurodegenerative disorders. Growing data suggested that overconsumption of high-fat/high-carbohydrates diet (HFHCD) is associated with enhanced incidence of metabolic alterations, neurodegeneration, and cognitive dysfunction. Functional foods have gained prominence in curbing metabolic and neurological deficits.
View Article and Find Full Text PDFBiomedicines
January 2025
Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima 28045, Colima, Mexico.
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January 2025
Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, USA. Electronic address:
The astroglial glutamate transporter in the hippocampus and anterior cingulate cortex (ACC) is critically involved in chronic pain-induced cognitive and psychiatric abnormalities. We have previously reported that LDN-212320, a glutamate transporter-1 (GLT-1) activator, attenuates complete Freund's adjuvant (CFA)-induced acute and chronic nociceptive pain. However, the cellular and molecular mechanisms underlying GLT-1 modulation in the hippocampus and ACC during chronic pain-induced cognitive deficit-like and anxiety-like behaviors remain unknown.
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