Prenatal exposure to the CB1 and CB2 cannabinoid receptor agonist WIN 55,212-2 alters migration of early-born glutamatergic neurons and GABAergic interneurons in the rat cerebral cortex

Authors

  • Trinidad M. M. Saez,

    Corresponding author
    1. Instituto de Biología Celular y Neurociencia "Prof. E. De Robertis" (IBCN), UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
    • Address correspondence and reprint requests to Trinidad María de los Milagros Saez, Instituto de Biología Celular y Neurociencia "Prof. E. De Robertis" (IBCN), UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, C1121ABG, Ciudad Autónoma de Buenos Aires, Argentina. E-mail: trinidad.mm.saez@gmail.com

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  • María P. Aronne,

    1. Instituto de Biología Celular y Neurociencia "Prof. E. De Robertis" (IBCN), UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
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  • Laura Caltana,

    1. Instituto de Biología Celular y Neurociencia "Prof. E. De Robertis" (IBCN), UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
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  • Alicia H. Brusco

    1. Instituto de Biología Celular y Neurociencia "Prof. E. De Robertis" (IBCN), UBA-CONICET, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
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Abstract

The endocannabinoid system, composed of cannabinoid receptors, endocannabinoids, and synthesis and degradation enzymes, is present since early stages of brain development. During this period, the endocannabinoid system is involved in the regulation of neural progenitor proliferation and specification as well as the migration and differentiation of pyramidal neurons and interneurons. Marijuana consumption during pregnancy represents a serious risk in relation to the fetal brain development since Δ9-tetrahidrocannabinol, the main active compound of cannabis, can reach the fetus through placenta and hemato-encephalic barrier. Cohort studies performed on children and adolescents of mothers who consumed marijuana during pregnancy reported cognitive and comportamental abnormalities. In the present study, we examined the expression of the cannabinoid receptor CB1R during corticogenesis in radially and tangentially migrating post-mitotic neurons. We found that prenatal exposure to WIN impaired tangential and radial migration of post-mitotic neurons in the dorsal pallium. In addition, we described alterations of two transcription factors associated with proliferating and newly post-mitotic glutamatergic cells in the dorsal pallium, Tbr1 and Tbr2, and disruption in the number of Cajal–Retzius cells. The present results contribute to the knowledge of neurobiological substrates that determine neuro-comportamental changes that will persist through post-natal life.

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During corticogenesis, the endocannabinoid system plays an important role in neural progenitor proliferation, specification, neuronal migration, and differentiation. Children prenatally exposed to marijuana have a significant impairment of higher cognitive functions. We showed in the present study that Prenatal WIN55,212-2 exposure alters radial and tangential migration and induces a delay in glutamatergic neurons differentiation in the embryonic rat cerebral cortex. The present results contribute to the knowledge on neurobiological substrates that determine neurobehavioral changes that will persist through post-natal life.

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