Abstract

THE EVALUATION OF HISTOLOGICAL CHANGES AND IMUNOHISTOCHEMICAL EXPRESSION OF AMYLOID PRECURSOR PROTEIN IN CEREBRAL AND CEREBELLAR CORTICES IN NEWBORN MICE AFTER PRENATAL EXPOSURE TO TRAMADOL

Thair M. Farhan*, Huda R. Kammona and Haider J. Mubarak

Abstract

Tramadol is a centrally acting analgesic that used to reliefmodereate to severe pain, its use in pregnancy is generally avoided, still little information available on its effect on the central nervous system development if taken during pregnancy. Amyloid precursor protein(APP) is expressed in many tissues including neurons, it play a major role in neuronal survival, synapse formation, and neuronal growth. This study implicated to demonstrate the changes in APP expression in cerebral and cerebellar cortices upon perinatal exposure to different doses of tramadol, with its effect on their normal histological features. A sample of 60 pregnant mice were divided into four groups (15 in each group), control group that received D.W daily intra peritoneally, and test groupssubdivided into (A,B,C) those received 40,60, and 80mg/kg of tramadoldaily intra peritoneally from the start of pregnancy. Cerebral and cerebellar cortices of one day newborn mice were prepared for paraffin sections for H & E, and anti- APP ab15272 imunohistochemical stain that assessed by Aperio scope image analysis software V9. Significant changes in histological features were seen include cerebral and cerebellaratrophy, vascular changes (dilatation and rupture of vessels, cortex hemorrhagic areas), apoptotic changes, changes in cellular layers of pyramidal cells in cerebral cortex and loss of purkinji cells layer in cerebellar cortex, also changes in choroid plexus vascular pattern of the 4th ventricle. APP protein expression showed significant changes among groups (assessed by ANOVA) and between groups (assessed by un-paired t-test) compared to control, except between group A versus control in cerebral cortex, and between control and group C of test groups, group B of test groups versus group C, and group B and C of test groups in cerebellar cortexat p≤0.05. These findings indicate the harmful effect of perinatal tramadol on the cerebral and cerebellar development specifically in higher doses, and this is associated with increase in APP expression which is proportional to the dose of treatment in a way to protect neuronal tissue and to trigger apoptosis.

Keywords: Cerebral Cortex, APP, Apoptosis.