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Volume 4, Issue 5 (Suppl) J Pharmacovigil 2016
ISSN:2329-6887 JP, an open access journal Pharmacovigilance Congress 2016
September 28-30, 2016
September 28-30, 2016 Toronto, Canada
6th Pharmacovigilance Congress
Léger C et al., J Pharmacovigil 2016, 4:5 (Suppl)
Prenatal exposure to alcohol impairs the long termintegrationofGABAinterneurons and the proteolytic
endothelial activity in mouse neonates
Léger C1, Hauchecorne M1, Dupré N1, Aligny C1, Leroux P1, Marret S1,2 and Gonzalez B J1
1Normady University, « NeoVasc » Laboratory, Inserm, IRIB, Rouen University, France
2Department of Neonatal Pediatrics and Intensive Care, Rouen Hospital, France
During brain development, the NMDA receptor exerts trophic activities and is required for a correct integration of GABAergic
interneurons. The literature informs us that a prenatal alcohol exposure impacts the glutamatergic transmission. It is now
established that brain vessels are involved in the migration of GABAergic neurons and we recently showed that endothelial cells
express NMDA receptors. In the present study, we hypothesized that in utero alcohol exposure might impact the cortical integration
of GABAergic neurons via an alteration of the endothelial cell activity. Using Gad67-GFP mice, we investigated the effects of a
prenatal alcohol exposure on the survival of GABAergic precursors, the activation of endothelial MMPs and tPA and the long
term integration of GABAergic neurons in the neocortex. Treatment of cortical slices from E15 fetuses with ethanol revealed no
significant modification of the apoptotic death. In contrast, both in situ and gel zymographies showed that alcohol markedly reduced
the proteolytic activities of MMP9 and tPA in cortical microvessels. These effects were mimicked by the NMDA antagonist MK801.
A long term follow-up of the GABAergic interneuron population revealed that a prenatal alcohol exposure increased the density of
cortical GABAergic neurons and GFP expression levels but decreased the density of primary dendrites per neuron. Altogether, these
findings support that a prenatal alcohol exposition disturbs the activity of vascular matrix proteases and the long term integration
of GAD67-GFP interneurons. They raised the question of long term effects of molecules with NMDA antagonist properties such as
anesthetics.
Biography
Cécile Leger works at Normady University, « NeoVasc » Laboratory, Inserm, IRIB, Rouen University, France.