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The type 1 cannabinoid receptor is highly expressed in embryonic cortical projection neurons and negatively regulates neurite growth in vitro

Authors

  • Tania Vitalis,

    1. CNRS-UMR 7637, Laboratoire de neurobiologie et diversité cellulaire, 10 rue Vauquelin, ESPCI, 75005 Paris, France
    2. INSERM U616, Hôpital de la Pitié-Salpétrière, Paris, France
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  • Jeanne Lainé,

    1. Laboratoire de Neurobiologie du Cervelet, Université Pierre et Marie Curie Paris 6, Faculté de Médecine Pitié Salpétrière, Paris, France
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  • Anne Simon,

    1. CNRS-UMR 7637, Laboratoire de neurobiologie et diversité cellulaire, 10 rue Vauquelin, ESPCI, 75005 Paris, France
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  • Alexandre Roland,

    1. CNRS-UMR 7637, Laboratoire de neurobiologie et diversité cellulaire, 10 rue Vauquelin, ESPCI, 75005 Paris, France
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  • Christophe Leterrier,

    1. CNRS-UMR 7637, Laboratoire de neurobiologie et diversité cellulaire, 10 rue Vauquelin, ESPCI, 75005 Paris, France
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    • *

      Present address: INSERM U641, Université de la Méditerranée, Faculté de Médecine Secteur-Nord, IFR 11, Marseille, F-13916 France.

  • Zsolt Lenkei

    1. CNRS-UMR 7637, Laboratoire de neurobiologie et diversité cellulaire, 10 rue Vauquelin, ESPCI, 75005 Paris, France
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Dr Z. Lenkei and Dr T. Vitalis, as above.
E-mail: zsolt.lenkei@espci.fr and tmvitalis@hotmail.com

Abstract

In the rodent and human embryonic brains, the cerebral cortex and hippocampus transiently express high levels of type 1 cannabinoid receptors (CB1Rs), at a developmental stage when these areas are composed mainly of glutamatergic neurons. However, the precise cellular and subcellular localization of CB1R expression as well as effects of CB1R modulation in this cell population remain largely unknown. We report that, starting from embryonic day 12.5, CB1Rs are strongly expressed in both reelin-expressing Cajal-Retzius cells and newly differentiated postmitotic glutamatergic neurons of the mouse telencephalon. CB1R protein is localized first to somato-dendritic endosomes and at later developmental stages it localizes mostly to developing axons. In young axons, CB1Rs are localized both to the axolemma and to large, often multivesicular endosomes. Acute maternal injection of agonist CP-55940 results in the relocation of receptors from axons to somato-dendritic endosomes, indicating the functional competence of embryonic CB1Rs. The adult phenotype of CB1R expression is established around postnatal day 5. By using pharmacological and mutational modulation of CB1R activity in isolated cultured rat hippocampal neurons, we also show that basal activation of CB1R acts as a negative regulatory signal for dendritogenesis, dendritic and axonal outgrowth, and branching. Together, the overall negative regulatory role in neurite development suggests that embryonic CB1R signaling may participate in the correct establishment of neuronal connectivity and suggests a possible mechanism for the development of reported glutamatergic dysfunction in the offspring following maternal cannabis consumption.

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