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Acute intrastriatal administration of quinolinic acid affects the expression of the coat protein AP-2 and its interaction with membranes

  • Basic Neurosciences, Genetics and Immunology - Original Article
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Abstract

Clathrin-coated vesicle endocytosis is thought to be crucial for the maintenance of synaptic transmission and for the cell plasticity at the nervous system. In this study, we demonstrated that acute intrastriatal administration of quinolinic acid (QUIN), an agonist of the N-methyl-d-aspartate receptor, induces a decrease of the coat protein AP-2 expression and affects their interaction with membranes. By western blot analysis we observed that at 24 h after QUIN intrastriatal injection, α1 subunit of AP-2 and α2, at lesser extent, were reduced in the striatal membranes. The decrease of both subunits expression was extended to 48 h after treatment, although the soluble proteins were mostly affected. Other areas of the brain were not affected by the treatment, except the cerebellum, where a significant increase of soluble AP-2 (both subunits) was observed at 48 h after injection. Another coat protein, as the phosphoprotein AP-180, was not affected by the injection of QUIN. We also confirmed that QUIN injection causes increasing loss of striatal neurons after the administration of the toxin. We concluded that QUIN may affect the endocytotic machinery of the striatum, by inducing changes in the AP-2 behaviour. Consequently, the internalization of NMDAR and/or AMPAR may be affected, by QUIN, contributing to the excitotoxic effect of the drug.

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Acknowledgments

This work was supported by grants from SECyT (UNCuyo-Argentina), the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina, and the VolksWagen Stiftung (Germany). We thank Mr. T. Sartor for the valuable technical assistance.

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Authors and Affiliations

  1. Laboratorio de Biología y Fisiología Celular “Dr. Francisco Bertini”, Instituto de Histología y Embriología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina

    Janina Borgonovo & Miguel Angel Sosa

  2. Laboratorio de Neurobiología, Instituto de Histología y Embriología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina

    Alicia Seltzer

  3. Instituto de Ciencias Básicas (ICB), Universidad Nacional de Cuyo, Mendoza, Argentina

    Miguel Angel Sosa

Authors
  1. Janina Borgonovo
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  2. Alicia Seltzer
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  3. Miguel Angel Sosa
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Correspondence to Miguel Angel Sosa.

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A. Seltzer and M. A. Sosa contributed equally to this article.

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Borgonovo, J., Seltzer, A. & Sosa, M.A. Acute intrastriatal administration of quinolinic acid affects the expression of the coat protein AP-2 and its interaction with membranes. J Neural Transm 116, 1201–1208 (2009). https://doi.org/10.1007/s00702-009-0262-5

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  • DOI: https://doi.org/10.1007/s00702-009-0262-5

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