Overexpression of the Immunoreceptor CD300f Has a Neuroprotective Role in a Model of Acute Brain Injury

Authors

  • Hugo Peluffo,

    Corresponding author
    1. Department of Histology and Embryology, Faculty of Medicine, UDELAR, Montevideo, Uruguay.
    2. Neurodegeneration Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay.
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  • Daniela Alí-Ruiz,

    1. Department of Histology and Embryology, Faculty of Medicine, UDELAR, Montevideo, Uruguay.
    2. Neurodegeneration Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay.
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  • Aroa Ejarque-Ortíz,

    1. Immunobiology Group, CIBBIM-Nanomedicine Program, Hospital Universitari Vall d'Hebrón, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
    2. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III.
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  • Victor Heras-Alvarez,

    1. Immunobiology Group, CIBBIM-Nanomedicine Program, Hospital Universitari Vall d'Hebrón, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
    2. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III.
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  • Emma Comas-Casellas,

    1. Immunobiology Group, CIBBIM-Nanomedicine Program, Hospital Universitari Vall d'Hebrón, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
    2. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III.
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  • Agueda Martínez-Barriocanal,

    1. Immunobiology Group, CIBBIM-Nanomedicine Program, Hospital Universitari Vall d'Hebrón, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
    2. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III.
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  • Andres Kamaid,

    1. Department of Histology and Embryology, Faculty of Medicine, UDELAR, Montevideo, Uruguay.
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    • A. Kamaid is currently in: Departamento de Biología Celular y del Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México

  • Damiana Alvarez-Errico,

    1. Unitat de Bioquímica, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.
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  • Maria Luciana Negro,

    1. Department of Histology and Embryology, Faculty of Medicine, UDELAR, Montevideo, Uruguay.
    2. Neurodegeneration Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay.
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  • Natalia Lago,

    1. Neurodegeneration Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay.
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  • Simó Schwartz Jr,

    1. Drug Delivery and Targeting Group, CIBBIM-Nanomedicine Program, Hospital Universitari Vall d'Hebrón, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
    2. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III.
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  • Antonio Villaverde,

    1. Institute for Biotechnology and Biomedicine, Barcelona, Spain.
    2. Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, Barcelona, Spain.
    3. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III.
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  • Joan Sayós

    1. Immunobiology Group, CIBBIM-Nanomedicine Program, Hospital Universitari Vall d'Hebrón, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
    2. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III.
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Hugo Peluffo, PhD, Neurodegeneration Laboratory, Institut Pasteur de Montevideo, Calle Mataojo 2020, CP 11400, Montevideo, Uruguay (E-mail: hugo.peluffo@pasteur.edu.uy)

Abstract

It is well known that cell surface immune receptors play a critical role in regulating immune and inflammatory processes in the central nervous system (CNS). We have analyzed the function of cluster of differentiation (CD)300f immunoreceptor in a model of excitotoxic rat brain damage. First, to explore the presence of endogenous ligand(s) for this receptor we used a human CD300f-Ig soluble protein and confocal microscopy, showing specific staining mainly in CNS white matter and on the surface of oligodendrocytes and certain astrocytes. Next, we demonstrated in a model of in vivo rat brain excitotoxic damage that the overexpression of human CD300f induced a significant reduction in the lesion volume. To validate these results, we cloned the rat ortholog of CD300f protein (rCD300f). The overexpression of rCD300f receptor had a comparable neuroprotective effect after the acute brain injury and a similar CNS staining pattern when stained with the rCD300f-Ig soluble protein. Interestingly, when we analyzed the expression pattern of rCD300f in brain cells by quantitative polymerase chain reaction and immunohistochemistry, we detected the expression of CD300f as expected in microglial cells, but also in oligodendrocytes and neurons. These data suggest that the neuroprotective role of CD300f would be the result of a complex network of cell interactions.

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