TREATMENT WITH SILDENAFIL PREVENTS IMPAIRMENT OF LEARNING IN RATS BORN TO PRE-ECLAMPTIC MOTHERS

Pre-eclampsia is an important hypertensive pregnancy disorder and a main cause of maternal and fetal morbidity and mortality Children born from mothers with preeclampsia may present cognitive deficits The mechanisms leading to this cognitive impairment remain unclear and no treatments to improve it have been tested Pre-eclampsia is associated with impaired regulation of the nitric oxide 3 5 guanosine monophosphate cyclic (cGMP) pathway, which modulates some cognitive functions We hypothesized that alterations in the NO-cGMP pathway would be involved in the mechanisms leading to cognitive impairment in rats born to pre-eclamptic mothers and that treatment with sildenafil an inhibitor of the phosphodiesterase that degrades cGMP, could restore their cognitive function To test these hypotheses, we used an animal model of pre eclampsia in rats pregnant rats treated with L nitro arginine methyl ester, an inhibitor of nitric oxide synthase Using this model, we assessed (1) whether rats born to pre eclamptic mothers show reduced learning ability and/or altered motor activity or coordination when they are 2 months old, (2) whether cognitive impairment is associated with reduced function of the glutamate NO cGMP pathway in brain in vivo, and (3) whether treatment of the mothers with sildenafil prevents this cognitive and motor alterations The results reported show that the ability to learn a conditional discrimination task in a Y maze is reduced in rats born to pre eclamptic mothers This impairment was associated with reduced function of the glutamate NO cGMP pathway in brain in vivo as assessed by microdialysis in freely moving rats Treatment with sildenafil restores the function of this pathway and learning ability (C) 2010 IBRO Published by Elsevier Ltd All rights reserved