Deltamethrin induces hippocampal neuronal MEK/ERK signaling pathway and apoptosis leading to neurobehavioral disorders in mice

Objective To investigate the potential role and molecular mechanisms of the MEK/ERK signaling pathway and apoptosis in the neurotoxicity induced by short-term exposure to deltamethrin (DM).

Methods Forty adult male C57BL/6J mice were randomly divided into control group, low-dose DM group (4.5 mg/kg), medium-dose DM group (9.0 mg/kg), and high-dose DM group (18.0 mg/kg). The mice were intragastrically administered for 30 days consecutively, and the control group was administered an equivalent volume of corn oil. Learning and memory abilities of mice were assessed using the Morris water maze (MWM). The pathological changes of hippocampal neurons in the mice were observed through hematoxylin and eosin (HE) staining and Nissl staining. The expression of MEK1/2 and ERK1/2 was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and the protein expression of Bax, cytochrome c (Cyt-c), Cleaved Caspase3, Caspase3, MEK1/2, p-MEK, ERK1/2, and p-ERK were detected by western blotting.

Results The high-dose DM group showed a significantly different escape latency period compared to the control group (P < 0.05), while both the medium- and high-dose DM groups exhibited significantly reduced platform crossing times (P < 0.05). HE and Nissl staining revealed degeneration, necrosis, and a reduction in Nissl bodies in hippocampal neurons across all DM doses groups compared to the control group. The protein expression levels of Bax, Cyt-c, and Cl Caspase3/Caspase3 were significantly elevated in the DM dose groups compared to the control group (P < 0.05). The mRNA expression levels of MEK1 and ERK2 were significantly up-regulated in the high-dose DM group compared to the control group, whereas the mRNA expression levels of MEK2 and ERK1 were significantly downregulated in the medium- and high-dose DM groups (all P < 0.05). In terms of protein expression, p-MEK/MEK1/ 2 expression was increased in the medium- and high-dose DM groups, while p-ERK/ERK1/2 expression was decreased in the high-dose DM group (P < 0.05).

Conclusion Short-term oral exposure to DM can induce neurobehavioral abnormalities in mice and hippocampal neuronal damage-induced cell apoptosis. The underlying mechanism may be associated with the aberrant activation of the MEK/ERK signaling pathway.