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Integrity of White Matter is Compromised in Mice with Hyaluronan Deficiency.
Sherpa, Ang D; Guilfoyle, David N; Naik, Aditi A; Isakovic, Jasmina; Irie, Fumitoshi; Yamaguchi, Yu; Hrabe, Jan; Aoki, Chiye; Hrabetova, Sabina.
Afiliación
  • Sherpa AD; Center for Neural Science, New York University, 4 Washington Place, New York, NY, 10003, USA.
  • Guilfoyle DN; Department of Neurosurgery, New York University School of Medicine, 550 First Avenue, New York, NY, 10016, USA.
  • Naik AA; Medical Physics Laboratory, Center for Biomedical Imaging and Neuromodulation, Nathan S. Kline Institute, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA.
  • Isakovic J; Center for Neural Science, New York University, 4 Washington Place, New York, NY, 10003, USA.
  • Irie F; Department of Biology, New York University, 100 Washington Square East, 1009 Silver Center, New York, NY, 10003, USA.
  • Yamaguchi Y; Neural and Behavioral Science Graduate Program, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY, 11203, USA.
  • Hrabe J; Department of Cell Biology, State University of New York Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY, 11203, USA.
  • Aoki C; Center for Neural Science, New York University, 4 Washington Place, New York, NY, 10003, USA.
  • Hrabetova S; Omnion Research International, Ul. Mirka Deanovica 9, 10000, Zagreb, Croatia.
Neurochem Res ; 45(1): 53-67, 2020 Jan.
Article en En | MEDLINE | ID: mdl-31175541
Brain white matter is the means of efficient signal propagation in brain and its dysfunction is associated with many neurological disorders. We studied the effect of hyaluronan deficiency on the integrity of myelin in murine corpus callosum. Conditional knockout mice lacking the hyaluronan synthase 2 were compared with control mice. Ultrastructural analysis by electron microscopy revealed a higher proportion of myelin lamellae intruding into axons of knockout mice, along with significantly slimmer axons (excluding myelin sheath thickness), lower g-ratios, and frequent loosening of the myelin wrappings, even though the myelin thickness was similar across the genotypes. Analysis of extracellular diffusion of a small marker molecule tetramethylammonium (74 MW) in brain slices prepared from corpus callosum showed that the extracellular space volume increased significantly in the knockout animals. Despite this vastly enlarged volume, extracellular diffusion rates were significantly reduced, indicating that the compromised myelin wrappings expose more complex geometric structure than the healthy ones. This finding was confirmed in vivo by diffusion-weighted magnetic resonance imaging. Magnetic resonance spectroscopy suggested that water was released from within the myelin sheaths. Our results indicate that hyaluronan is essential for the correct formation of tight myelin wrappings around the axons in white matter.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Sustancia Blanca / Ácido Hialurónico Límite: Animals Idioma: En Revista: Neurochem Res Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Sustancia Blanca / Ácido Hialurónico Límite: Animals Idioma: En Revista: Neurochem Res Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos