The Developmental Neurotoxicity of Paracetamol – Evaluation of markers involved in brain development in mice

University essay from Uppsala universitet/Institutionen för farmaceutisk biovetenskap

Author: Armine Yakub; [2020]

Keywords: paracetamol; Neurotoxicity; mice;

Abstract: Paracetamol is a widely used non-prescription analgesic and antipyretic. Despite its wide usage, the mechanism of action of paracetamol is not fully known. It has been found that paracetamol interacts with the central cyclooxygenase system which is likely responsible for its antipyreticeffect whereas the analgesic effect of paracetamol mainly depends on cannabinoid receptor type 1 activation. Paracetamol is considered the first choice for treatment of pain and/or fever during pregnancy and can reach the developing brain following consumption since it crosses both blood-brain and placental barriers. However, increasing evidence from both animal and human studies show that developmental paracetamol exposure is associated with adverse behavioural outcomes later in life. Nonetheless, the mechanism behind paracetamol neurotoxicity is still unknown. The main aim of this study was to investigate whether adult mice neonatally exposed to paracetamol during a critical period of brain development known as brain growth spurt havealtered expression of biomarkers important for brain development. Mice were exposed to either paracetamol (30 + 30 mg / kg, 4-hour interval) or saline on postnatal day 10. The mice's brains were then dissected out when they were two months old. In this study, the brains were cryosectioned and examined by immunohistochemistry. This study shows that there is no significant difference in the protein levels of synaptophysin (SYP), a marker for synaptic density, in Cornu Ammonis subfield 3 (also known as CA3), Cornu Ammonis subfield 1 (also known as CA1), and dentate gyrus (DG) regions of adult hippocampus between paracetamol treated mice and controls. These findings suggest that previously observed adult behavioural changes after neonatal exposure to paracetamol may have other origins than effects on synaptic density using SYP marker. Further research on possible mechanisms behind paracetamol-induced adverse developmental effects is needed. 

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