title: 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.
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 Δ(9) -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 CB1 R 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.
authors: 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.
authors: Trinidad M M
authors: TM
authors: Saez
authors: María P
authors: MP
authors: Aronne
authors: Laura
authors: L
authors: Caltana
authors: Alicia H
authors: AH
authors: Brusco
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D048588:Benzoxazines / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D015816:Cell Adhesion Molecules, Neuronal / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects / Q000196:embryology; D000089622:Doublecortin Domain Proteins; D063388:Endocannabinoids / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000032:analysis; D005260:Female; D059330:GABAergic Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D007395:Interneurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000032:analysis; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009479:Neuropeptides / Q000032:analysis; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000096:biosynthesis / Q000502:physiology*; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000032:analysis; D020825:T-Box Domain Proteins / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D015816:Cell Adhesion Molecules, Neuronal; D000089622:Doublecortin Domain Proteins; D063388:Endocannabinoids; D016326:Extracellular Matrix Proteins; D008869:Microtubule-Associated Proteins; D009025:Morpholines; D009281:Naphthalenes; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D043884:Receptor, Cannabinoid, CB1; D000091042:Reelin Protein; D020825:T-Box Domain Proteins; C540454:Tbr1 protein, rat; D018698:Glutamic Acid; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D012697:Serine Endopeptidases
keywords: CB1 receptor; cannabinoid; developing cerebral cortex; post-mitotic migrating neurons; prenatal exposure