Fig. 8

The schematic diagram illustrates the impact of targeted activation of ErbB4 receptor on hippocampal neuronal damage, neuroinflammation, and cognitive functions in mice exposed to PS-MPs. The small molecule ErbB4 receptor agonist (E4A) binds to the ErbB4 receptor, initiating its downstream signaling pathway. This activation leads to the upregulation of SIRT3 protein expression, which enhances mitochondrial redox homeostasis, increases ATP production, and ameliorates mitochondrial dysfunction. Additionally, there is an upregulation of synaptic-related proteins, which contributes to the repair of synaptic damage and enhancement of synaptic function. As hippocampal neuronal function improves, the activation of the TLR4 receptor by pro-inflammatory factors in microglia is reduced, resulting in diminished phosphorylation of NF-κB and decreased activation of the NLRP3 inflammasome towards Caspase-1. Consequently, there is a reduction in the conversion of the IL-1β precursor to its mature form, thereby alleviating hippocampal neuroinflammation and ultimately enhancing the learning and cognitive functions of PS-MPs-exposed mice. The diagram was created with MedPeer (www.medpeer.cn)