Impact of tadalafil therapy during pregnancy on cognitive function of preeclamptic rats

Introduction and Objectives: Preeclampsia is a rare hypertensive pregnancy disorder associated with cognitive deterioration and memory impairment in women. Recent studies have shown that phosphodiesterase type ۵ (PDE۵) inhibitory drugs such as tadalafil may be useful in treating hypertension during pregnancy. Here, in the present study, we aimed to investigate the impact of tadalafil on cognitive function in the surgically reduced uteroplacental perfusion (RUPP) rat preeclampsia model.Methods: A total of ۴۲ timed pregnant Wistar rats were randomly allocated into four groups: control (n=۸), sham (n=۱۰), RUPP (n=۱۲), and RUPP treated with tadalafil (RUPP+Tad, n=۱۲). RUPP or sham procedures were performed on day ۱۴ of gestation. Tadalafil at the dose of ۱۰mg/kg was administrated orally to RUPP+Tad rats from gestational day ۱۴ (۴-hour after RUPP induction) to gestational day ۲۰ once per day. Instead, other studied groups were gavaged with ۰.۹% normal saline. The spatial learning and memory abilities were evaluated by the Morris water maze test on the ۳۰th day after parturition. Furthermore, the expression and localization of GluA۱-containing AMPA-type glutamate receptors subunit in their hippocampi were investigated immunohistochemically.Results: The RUPP procedure could successfully establish preeclampsia in rats by increasing blood pressure, proteinuria, and offspring with intrauterine growth restriction (lower birth weight than their peers in the sham group). RUPP dams exhibited impaired spatial learning ability and memory function in the Morris water maze accompanied by hippocampal downregulation of GluA۱-containing AMPA-Rs in the CA۱ and dentate gyrus (DG) hippocampal subfields. Tadalafil therapy improved learning ability in RUPP rats, but had no effects on impaired memory and hippocampal expression of GluA۱-containing AMPA-Rs.Conclusion: Tadalafil therapy during pregnancy through a mechanism independent of AMPA-type glutamate receptors synaptic transmission can resolve impaired spatial learning in preeclamptic rats.

کلیدواژه ها:

Preeclampsia ، Cognitive function ، AMPA receptors ، Tadalafil