Astaxanthin reduces TBPH-induced neurobehavioral deficits in mice by the ROS-ERK1/2-FOS pathway

Abstract

The persistence of the novel brominated flame retardant, bis(2-ethylhexyl)-3,4,5,6-tetrabromophthalate (TBPH), in the environment and its potential for bioaccumulation in living organisms, including humans, further exacerbate its health risks. Therefore, ongoing research is crucial for fully understanding the extent of TBPH’s neurotoxicity and for developing effective mitigation strategies. This study aims to investigate the potential neurotoxicity of TBPH on mouse neurobehavior and to evaluate the protective effects of the natural antioxidant astaxanthin (AST) against TBPH-induced neurotoxicity. The results indicate that exposure to TBPH can lead to a decline in learning and memory abilities and abnormal behaviors in mice, which may be associated with oxidative stress responses and apoptosis in the hippocampus. TBPH may disrupt the normal function of hippocampal neurons by activating the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. Mice exposed to TBPH treated with AST showed improved learning and memory abilities in the Morris water maze (MWM) and Step-down test (SDT). AST, through its antioxidant action, was able to significantly reduce the increase in reactive oxygen species (ROS) levels induced by TBPH, the increased expression of apoptosis markers, and the activation of the ERK1/2-FOS signaling pathway, alleviating TBPH-induced apoptosis in hippocampal neurons and improving neurobehavioral outcomes. These findings suggest that AST may alleviate the neurotoxicity of TBPH by modulating molecular events related to apoptosis and the ERK1/2-FOS signaling pathway. Thus, this study provides evidence for AST as a potential interventional strategy for the prevention or treatment of cognitive decline associated with environmental neurotoxicant exposure.

Keywords

• Astaxanthin
• TBPH
• Hippocampal neuron apoptosis
• ERK1/2-FOS pathway