Consequences of prenatal exposure to cannabinoid agonist on the distribution of postmitotic neuroblastsn and projection neurons in the developing cerebral cortex

SAEZ, TRINIDAD; BRUSCO, ALICIA

Uspallata, Mendoza

Congreso; V Neurotoxicity Society Meeting; 2011

Neurotoxicity Society

The endocannabinoid system plays a modulatory role in specific processes of brain development such as radial and tangential migration and cell proliferation. Neurons of the cerebral cortex derive from two sources: projection neurons, which migrate radially from the neuroepithelium of the dorsal pallium and interneurons, which migrate tangentially from the ganglionic eminence. Cajal-Retzius (CR) cells are the earliest generated cortical neurons and migrate from the borders of the developing pallium. Doublecortin is a microtubule-associated protein expressed in postmitotic neurons during periods of migration. First, we studied the expression of cannabinoid receptor CB1 on postmitotic neuroblasts in the fetal cerebral cortex and Ganglionic Eminence at embryonic days 12, 13, 14, 15 and 16. The aim of this study was to assess the effects of prenatal exposure to cannabinoid CB1/CB2 receptor agonist WIN55,212-2 (WIN) on postmitotic neuroblast, postmitotic projection neurons, C-R cells and cell proliferation in the fetal cerebral cortex. Pregnant Wistar rats were treated, from gestational day 5 to 16, at a daily s.c. WIN dose (0.75mg/kg). WIN-exposed rats showed altered distribution and orientation of tangential and radial migrating postmitotic neuroblast (cells Doublecortin+) and also the radial distribution of postmitotic projections neurons (cells tbr1+) along the Cortical Plate. No changes were observed in number of proliferating cells in the ventricular zone. Prenatal exposure to WIN increase the number of CR cells in the marginal zone. The effects of cannabinoids on cortical development may by due to its effects on the generation and/or migration of neuroblasts and postmitotic projection neurons.