Cannabinoid agonist alters the distribution of radial and tangential migrating postmitotic neuroblast and early-born glutamatergic neurons in the fetal cerebral cortex

SAEZ, TRINIDAD; BRUSCO, ALICIA

Washington

Congreso; 41 Meeting of the Society for Neuroscience; 2011

Society for Neuroscience

Marihuana is one of the most commonly abused illicit drugs among pregnant women. Since theendocannabinoid system (eCBs) plays a key modulatory role in specific processes of braindevelopment, such as neural progenitor proliferation, neuronal migration and specification, it isexpectable that manipulations of the eCBs by exposure to cannabinoids (CB) during earlydevelopmental stages can result in long-lasting neurobehavioural consequences. The impact of CB onthe developing brain is still not well understood. Neurons of the cerebral cortex derive from twosources: projection neurons, which migrate radially from the neuroepithelium of the dorsal pallium andinterneurons, which migrate tangentially from the ganglionic eminence (GE). Cajal-Retzius (CR) cellsare the earliest generated cortical neurons and plays a critical rol in the proper laminar positioning ofmigration projection neurons by secreting the extracellular gycoprotein reelin. Pregnant Wistar ratsreceived 0.75mg/kg of the cannabinoid CB1 receptor agonist WIN55212-2 (WIN) from gestational day5 to 16. Orientation and distribution of migrating postmitotic neuroblasts were examined by measuringthe migration angle of the leading process and counting doublecourtin (DCX) + cells in 3 sectorsthroughout the cerebral cortex at embrionyc day 16.5 (E16.5). WIN-exposed rats showed altereddistribution and orientation of tangential and radial migrating postmitotic neuroblasts along thedeveloping cerebral cortex. There was a significant increase in the proportion of tangential and radialcells near of GE combined with a decrease in farthest sectors. The radial distribution of glutamatergicearly-born cortical neurons along the cortical plate was quantified by measuring the distance of eachTbr1+ cell to the pial basement membrane. Prenatal WIN exposure alters the radial distribution ofTbr1+ cells in the developing cerebral cortex at E14.5. Moreover, cannabinoid exposure duringpregnancy increase the number of Reelin-immunoreactive cells (CR cells) at E14.5 and E16.5. Nochanges were observed in the number of proliferating cells (Ki67+ cells) in the ventricular zone at bothages. These results suggest the prescence of alterations in the tangencial and radial migration ofneuroblasts and postmitotic projection neurons. These findings are important in understanding thelong-term consequences of alterations in CB1R activity during development, frequently described inchildren and adolescents whose mothers smoked marihuana during pregnancy.