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Long-term alterations in μ, δ and κ opioidergic receptors following middle cerebral artery occlusion in mice

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Abstract

Alterations in the opioidergic system may play a role in the molecular mechanisms underlying neurochemical responses to cerebral ischaemia. The present study aimed to determine the delayed expression of μ, δ and κ opioid receptors, following 1, 2, 7, and 30 days of middle cerebral artery occlusion (MCAO) in mice. Using quantitative autoradiography, we highlighted significant decreases in μ, δ and κ opioid receptor expression in ipsilateral cortices from day 1 post-MCAO. Moreover, in contralateral nucleus lateralis thalami pars posterior, ipsi- and contralateral nucleus medialis dorsalis thalami, and ipsilateral substantia nigra, pars reticulata (SNr), κ receptors were increased; μ receptor densities were decreased in nucleus ventralis thalami, pars posterior (VThP), and SNr. δ-Binding sites were increased in the striatum on day 30 post-MCAO. The alterations in opioid receptors in cortical infarcts were correlated with strong histological damage. Further reductions in opioid receptor densities in cortical infarcts were observed at later time points. In subcortical brain regions, opioid receptor densities were also altered but no histological damage was seen, except in the VThP, in which cell density was increased on day 30. Delayed reductions in opioid receptor densities in the infarct appeared as the continuation of the early processes previously demonstrated. However, changes in subcortical opioid receptor expression may correlate with neuronal alterations in remote brain regions. Changes in opioidergic receptor expression in these regions may be involved in the long-term consequences of stroke and could be used as biomarker of neuronal alteration through the use of imaging techniques in the clinic.

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Acknowledgments

This study was supported by the University of Caen, the CNRS and the “Fondation pour la Recherche Médicale”. The authors wish to thank Didier DIVOUX, and Drs. Hélène NALLET, Michel BOULOUARD, Simon ROUSSEL, Omar TOUZANI, Antonio RUOCCO and Alan R. YOUNG for their contribution to the blind analysis of histological damage and Florence MEZENGE and Nicole JACQUES for their kind technical help. The authors wish to thank Drs Alan R. YOUNG, Barry McCOLL and Peter THORNTON for their help in the review of this manuscript.

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Authors and Affiliations

  1. CNRS UMR 6185, Centre CYCERON, Caen, France

    Hervé Boutin, Armelle Catherine, Eric T. MacKenzie & Philippe Jauzac

  2. UPRES EA3915, CERMN, Département de Pharmacologie–Physiologie de l’UFR des Sciences Pharmaceutiques, Université de Caen, Basse Normandie, Caen, France

    François Dauphin

  3. Faculty of Life Sciences, Michael Smith Building, University of Manchester, Oxford road, Manchester, M13-9PT, UK

    Hervé Boutin

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  1. Hervé Boutin
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  2. Armelle Catherine
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Correspondence to Hervé Boutin.

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Boutin, H., Catherine, A., MacKenzie, E.T. et al. Long-term alterations in μ, δ and κ opioidergic receptors following middle cerebral artery occlusion in mice. Acta Neuropathol 114, 491–500 (2007). https://doi.org/10.1007/s00401-007-0269-7

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