Reduced extracellular space in the brain of tenascin-R- and HNK-1-sulphotransferase deficient mice

Authors

  • Eva Syková,

    1. Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20 Prague 4, Czech Republic
    2. Department of Neuroscience and Center for Cell Therapy and Tissue Repair, Charles University, 2nd Medical Faculty, V úvalu 84, 150 06 Prague 5, Czech Republic
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  • Ivan Voříšek,

    1. Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20 Prague 4, Czech Republic
    2. Department of Neuroscience and Center for Cell Therapy and Tissue Repair, Charles University, 2nd Medical Faculty, V úvalu 84, 150 06 Prague 5, Czech Republic
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  • Tomáš Mazel,

    1. Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20 Prague 4, Czech Republic
    2. Department of Neuroscience and Center for Cell Therapy and Tissue Repair, Charles University, 2nd Medical Faculty, V úvalu 84, 150 06 Prague 5, Czech Republic
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  • Tatiana Antonova,

    1. Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20 Prague 4, Czech Republic
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    • This paper is dedicated to Tatiana Antonova, recently deceased, who made a significant contribution to this study.

  • Melitta Schachner

    1. Zentrum für Molekulare Neurobiologie, University of Hamburg, Falkenried 94, D-20251, Hamburg, Germany
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Professor E. Syková, 1Institute of Experimental Medicine, as above.
E-mail: sykova@biomed.cas.cz

Abstract

Tenascin-R (TN-R), a large extracellular glycoprotein, is an important component of the adult brain's extracellular matrix (ECM); tenascin-C (TN-C) is expressed mainly during early development, while human natural killer 1 (HNK-1) is a sulphated carbohydrate epitope that attaches to these molecules, modifying their adhesive properties. To assess their influence on extracellular space (ECS) volume and geometry, we used the real-time iontophoretic method to measure ECS volume fraction α and tortuosity λ, and diffusion-weighted magnetic resonance imaging (MRI) to measure the apparent diffusion coefficient of water (ADCW). Measurements were performed in vivo in the cortex and CA1 hippocampal region of TN-R-, TN-C- and HNK-1 sulphotransferase (ST)-deficient adult mice and their wild-type littermate controls. In both cortex and hippocampus, the lack of TN-R or HNK-1 sulphotransferase resulted in a significant decrease in α and λ. Compared with controls, α in TN-R–/– and ST–/– mice decreased by 22–26% and 9–15%, respectively. MRI measurements revealed a decreased ADCW in the cortex, hippocampus and thalamus. ADCW reflected the changes in α; the decrease in λ indicated fewer diffusion obstacles in the ECS, presumably due to a decreased macromolecular content. No significant changes were found in TN-C–/– animals. We conclude that in TN-R–/– and ST–/– mice, which show morphological, electrophysiological and behavioural abnormalities, the ECS is reduced and its geometry altered. TN-R, as an important component of the ECM, appears to maintain an optimal distance between cells. The altered diffusion of neuroactive substances in the brain will inevitably affect extrasynaptic transmission, neuron–glia interactions and synaptic efficacy.

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