The role of ER/ERK/CREB pathway mediated mitophagy in bisphenol F-induced cognitive function changes in young female rats

Abstract

Bisphenol F (BPF) is a widespread industrial chemical and suspected neurotoxicant, yet its effects on cognitive function and the underlying mechanisms remain unclear. This study aimed to investigate whether BPF exposure induced cognitive function changes in young female rats were associated with ER/ERK/CREB pathway and subsequent mitophagy. 4-week-old Sprague-Dawley female rats received BPF via oral gavage (25 or 250 μg/kg bw/d) for 4 weeks. Cognitive function was evaluated using the Morris water maze and novel object recognition test during the last week of exposure. Hippocampal tissue was analysed for histomorphology, ER/ERK/CREB pathway changes, mitophagy and apoptosis. In this study, spatial learning in rats was transiently impaired, whereas long-term spatial memory remained unchanged in rats following BPF exposure. The recognition capability was improved as the dose increased. At the molecular level, the protein related to ER/ERK/CREB pathway, mitophagy and apoptosis were downregulated. Moreover, the mitophagy was downregulated in hippocampal CA1 region. These findings suggested that BPF exposure affected cognitive functions in young female rats, which was associated with the alterations of mitophagy mediated by ER/ERK/CREB pathway.