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Distribution of different isoforms of receptor protein tyrosine phosphatase γ (Ptprg-RPTP γ) in adult mouse brain: upregulation during neuroinflammation

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Abstract

The receptor protein tyrosine phosphatase γ (Ptprg-RPTPγ) is a receptor protein widely expressed in many tissues, including the central nervous system (CNS). Several RPTPγ isoforms are expressed in the brain during development and in adulthood, but their distribution and role are unknown. In this study, we investigated the distribution of some RPTPγ isoforms in the adult brain using antibodies against the epitopes localized in the C- and in the N-terminal domains of the full length isoform of RPTPγ. We found a predominant and widespread neuronal positivity throughout the neocortex, hippocampus, striatum and in many nuclei of the brainstem and cerebellum. At least 2 distinct isoforms that can co-exist in various compartments in the same cell are detectable in different neuron types. Immunopositivity for epitopes located in both the N- and C-terminus domains were found in the neuropil of cortical and hippocampal neurons, whereas the N-terminal domain positivity was found in the soma, often without colocalization with its C-terminal counterpart. Among glial cells, some protoplasmic and perivascular astrocytes and the cerebellar Bergmann glia, express RPTPγ. The astrocytic expression of RPTPγ and putative processing isoforms of 120 and 80 kDa increases during neuroinflammation, in particular 24 h after LPS treatment. Activated astrocytes were found to be strongly positive for RPTPγ also in a mice model of Alzheimer’s disease. Our results confirm previous findings and enrich the current knowledge of RPTPγ distribution in the CNS, highlighting a role of RPTPγ during neuroinflammation processes.

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Acknowledgments

This work was supported by University of Verona and Fondazione Cariverona-project Verona Nanomedicine Initiative. Development and characterization of antibodies were supported by AIRC IG 4667 and Consorzio per gli Studi Universitari, Verona.

Conflict of interest

The authors declare no competing financial interests.

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Authors and Affiliations

  1. Section of Physiology, Department of Neurological, Neuropsychological, Morphological and Motor Sciences, University of Verona, Strada le Grazie 8, 37134, Verona, Italy

    Erika Lorenzetto & Mario Buffelli

  2. Section of General Pathology, Department of Pathology and Diagnostics, University of Verona, Strada le Grazie 8, 37134, Verona, Italy

    Elisabetta Moratti, Marzia Vezzalini & Claudio Sorio

  3. Department of Neuroscience, Institut Pasteur of Paris, 25-28 rue du Dr Roux, 75624, Paris, France

    Sheila Harroch

  4. Center for Biomedical Computing, University of Verona, Strada le Grazie 8, 37134, Verona, Italy

    Mario Buffelli

  5. National Institute of Neuroscience, Verona, Italy

    Mario Buffelli

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  1. Erika Lorenzetto
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  2. Elisabetta Moratti
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  3. Marzia Vezzalini
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  4. Sheila Harroch
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  5. Claudio Sorio
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  6. Mario Buffelli
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Correspondence to Erika Lorenzetto or Mario Buffelli.

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As an additional test for antibody specificity we stained some slides from one heterozygous and one RPTPγ KO mouse using the two antibodies against the N- (ch-RPTPγ, green) and the C-terminus (goat-RPTPγ, red) epitopes of the phosphatase. Cerebral cortex (A–F and J–O) and hippocampus (G–I and P–R) showed a strong decrease of RPTPγ signal in the KO (J–R) in comparison to the heterozygous (A–I). A residual staining was still present in some regions, in particular in the granular layer of the hippocampus, a region known to be prone to aspecific staining. Scale bars 50 μm.

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Lorenzetto, E., Moratti, E., Vezzalini, M. et al. Distribution of different isoforms of receptor protein tyrosine phosphatase γ (Ptprg-RPTP γ) in adult mouse brain: upregulation during neuroinflammation. Brain Struct Funct 219, 875–890 (2014). https://doi.org/10.1007/s00429-013-0541-7

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