Ethanol modulation of cerebellar neuroinflammation in a postnatal mouse model of fetal alcohol spectrum disorders
| العنوان: | Ethanol modulation of cerebellar neuroinflammation in a postnatal mouse model of fetal alcohol spectrum disorders |
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| المؤلفون: | Paul D. Drew, Ania K. Majewska, Kevin D. Phelan, Jennifer W. Johnson, James C. Douglas, Tonya M. Rafferty, Cynthia J.M. Kane, Victoria M. Niedzwiedz-Massey |
| المصدر: | J Neurosci Res |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Cerebellum, Inflammasomes, NOS1, Gene Expression, Neuropathology, Article, Sholl analysis, Mice, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Pregnancy, medicine, Animals, Receptor, Neuroinflammation, Microglia, Chemokine CX3CL1, business.industry, Granule cell, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, Fetal Alcohol Spectrum Disorders, Neuroinflammatory Diseases, Cytokines, Female, business, Neuroscience, 030217 neurology & neurosurgery |
| الوصف: | Fetal alcohol spectrum disorders (FASD) are alarmingly common, result in significant personal and societal loss, and there is no effective treatment for these disorders. Cerebellar neuropathology is common in FASD and causes aberrant cognitive and motor function. Ethanol induced neuroinflammation is believed to contribute to neuropathological sequelae of FASD, and was previously demonstrated in the cerebellum in animal models of FASD. We now demonstrate neuroinflammation persists in the cerebellum several days following cessation of ethanol treatment in an early postnatal mouse model, with meaningful implications for timing of therapeutic intervention in FASD. We also demonstrate by Sholl analysis that ethanol decreases ramification of microglia cell processes in cells located near the Purkinje cell layer but not those near the external granule cell layer. Ethanol did not alter the expression of anti-inflammatory molecules or molecules that constitute NLRP1 and NLRP3 inflammasomes. Interestingly, ethanol decreased the expression of IL-23a (P19) and IL-12Rβ1 suggesting that ethanol may suppress IL-12 and IL-23 signaling. Fractalkine-fractalkine receptor (CX3CL1-CX3CR1) signaling is believed to suppress microglial activation and our demonstration that ethanol decreases CX3CL1 expression suggests that ethanol modulation of CX3CL1-CX3CR1 signaling may contribute to cerebellar neuroinflammation and neuropathology. We demonstrate ethanol alters the expression of specific molecules in the cerebellum understudied in FASD, but crucial for immune responses. Ethanol increases the expression of NOX-2 and NGP and decreases the expression of RAG1, NOS1, CD59a, S1PR5, PTPN22, GPR37, and Serpinb1b. These molecules represent a new horizon as potential targets for development of FASD therapy. |
| تدمد: | 1097-4547 0360-4012 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::65fa0c535ffa1000884fab734df73c4b https://doi.org/10.1002/jnr.24797 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....65fa0c535ffa1000884fab734df73c4b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10974547 03604012 |
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