Abstract: Objective To explore the effect of up-regulation of KA1 subunit of the kainate receptor on endoplasmic reticulum
stress (ERS)-induced excitotoxic neurodegeneration in mouse hippocampus. Methods Seventy adult male KM mice were
subjected to microinjections into the hippocampus of kainic acid (KA) or 500, 1000, or 2000 μg/ml tunicamycin (TM). At 1, 2, 3,
4, 5, 8, and 12 h after the injections, the mice were assessed for Bederson scores and sacrificed for FJB staining and
immunofluorescence observation of the brain slices. Results At 3, 4, 5, and 8 h after KA injection and at 4 and 5 h after of 2000
μg/ml TM injection, the mice showed severe central nervous system dysfunction, and FJB staining revealed increased cell
death in the hippocampus, where up-regulated expressions of KA1 receptor and ERS marker P-eIF2α were found by
immunofluorescence staining (P<0.05). Conclusion Microinjection of KA or TM into the hippocampus causes neuronal death
and ERS with up-regulated expression of KA1. In this process of neuronal apoptosis, the membrane receptor KA1 receives the
apoptosis signal and transfers it to the inside of the cells to cause cell endoplasmic reticulum dysfunction and ERS response,
which ultimately leads to neuronal death.