Sphingosine kinase 1 deficiency exacerbates LPS-induced neuroinflammation.

The pathogenesis of inflammation in the central nervous system (CNS), which contributes to numerous neurodegenerative diseases and results in encephalopathy and neuroinflammation, is poorly understood. Sphingolipid metabolism plays a crucial role in maintaining cellular processes in the CNS, and thu...

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Autores principales:	Natalia M Grin'kina, Eddy E Karnabi, Dushyant Damania, Sunil Wadgaonkar, Ilham A Muslimov, Raj Wadgaonkar
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a566820079814011b924fda304235c0e
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spelling	oai:doaj.org-article:a566820079814011b924fda304235c0e2021-11-18T07:18:24ZSphingosine kinase 1 deficiency exacerbates LPS-induced neuroinflammation.1932-620310.1371/journal.pone.0036475https://doaj.org/article/a566820079814011b924fda304235c0e2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22615770/?tool=EBIhttps://doaj.org/toc/1932-6203The pathogenesis of inflammation in the central nervous system (CNS), which contributes to numerous neurodegenerative diseases and results in encephalopathy and neuroinflammation, is poorly understood. Sphingolipid metabolism plays a crucial role in maintaining cellular processes in the CNS, and thus mediates the various pathological consequences of inflammation. For a better understanding of the role of sphingosine kinase activation during neuroinflammation, we developed a bacterial lipopolysaccharide (LPS)-induced brain injury model. The onset of the inflammatory response was observed beginning 4 hours after intracerebral injection of LPS into the lateral ventricles of the brain. A comparison of established neuroinflammatory parameters such as white matter rarefactions, development of cytotoxic edema, astrogliosis, loss of oligodendrocytes, and major cytokines levels in wild type and knockout mice suggested that the neuroinflammatory response in SphK1-/- mice was significantly upregulated. At 6 hours after intracerebroventricular injection of LPS in SphK1-/- mice, the immunoreactivity of the microglia markers and astrocyte marker glial fibrillary acidic protein (GFAP) were significantly increased, while the oligodendrocyte marker O4 was decreased compared to WT mice. Furthermore, western blotting data showed increased levels of GFAP. These results suggest that SphK1 activation is involved in the regulation of LPS induced brain injury. RESEARCH HIGHLIGHTS: • Lipopolysaccharide (LPS) intracerebral injection induces severe neuroinflammation. • Sphingosine kinase 1 deletion worsens the effect of the LPS. • Overexpression of SphK1 might be a potential new treatment approach to neuroinflammation.Natalia M Grin'kinaEddy E KarnabiDushyant DamaniaSunil WadgaonkarIlham A MuslimovRaj WadgaonkarPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e36475 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Natalia M Grin'kina Eddy E Karnabi Dushyant Damania Sunil Wadgaonkar Ilham A Muslimov Raj Wadgaonkar Sphingosine kinase 1 deficiency exacerbates LPS-induced neuroinflammation.
description	The pathogenesis of inflammation in the central nervous system (CNS), which contributes to numerous neurodegenerative diseases and results in encephalopathy and neuroinflammation, is poorly understood. Sphingolipid metabolism plays a crucial role in maintaining cellular processes in the CNS, and thus mediates the various pathological consequences of inflammation. For a better understanding of the role of sphingosine kinase activation during neuroinflammation, we developed a bacterial lipopolysaccharide (LPS)-induced brain injury model. The onset of the inflammatory response was observed beginning 4 hours after intracerebral injection of LPS into the lateral ventricles of the brain. A comparison of established neuroinflammatory parameters such as white matter rarefactions, development of cytotoxic edema, astrogliosis, loss of oligodendrocytes, and major cytokines levels in wild type and knockout mice suggested that the neuroinflammatory response in SphK1-/- mice was significantly upregulated. At 6 hours after intracerebroventricular injection of LPS in SphK1-/- mice, the immunoreactivity of the microglia markers and astrocyte marker glial fibrillary acidic protein (GFAP) were significantly increased, while the oligodendrocyte marker O4 was decreased compared to WT mice. Furthermore, western blotting data showed increased levels of GFAP. These results suggest that SphK1 activation is involved in the regulation of LPS induced brain injury. RESEARCH HIGHLIGHTS: • Lipopolysaccharide (LPS) intracerebral injection induces severe neuroinflammation. • Sphingosine kinase 1 deletion worsens the effect of the LPS. • Overexpression of SphK1 might be a potential new treatment approach to neuroinflammation.
format	article
author	Natalia M Grin'kina Eddy E Karnabi Dushyant Damania Sunil Wadgaonkar Ilham A Muslimov Raj Wadgaonkar
author_facet	Natalia M Grin'kina Eddy E Karnabi Dushyant Damania Sunil Wadgaonkar Ilham A Muslimov Raj Wadgaonkar
author_sort	Natalia M Grin'kina
title	Sphingosine kinase 1 deficiency exacerbates LPS-induced neuroinflammation.
title_short	Sphingosine kinase 1 deficiency exacerbates LPS-induced neuroinflammation.
title_full	Sphingosine kinase 1 deficiency exacerbates LPS-induced neuroinflammation.
title_fullStr	Sphingosine kinase 1 deficiency exacerbates LPS-induced neuroinflammation.
title_full_unstemmed	Sphingosine kinase 1 deficiency exacerbates LPS-induced neuroinflammation.
title_sort	sphingosine kinase 1 deficiency exacerbates lps-induced neuroinflammation.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/a566820079814011b924fda304235c0e
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Sphingosine kinase 1 deficiency exacerbates LPS-induced neuroinflammation.

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