Kainic Acid Treatment Increases Ca²⁺-mediated Neurotoxicity in the Mouse Hippocampus / 체질인류학회지

ABSTRACT

Kainic acid (KA)-induced neuronal cell death is associated with intracellular Ca²⁺ influx. However, it is unknown whether Lyn/Btk pathway is involved in the Ca²⁺-mediated neurotoxicity and neuronal death induced by KA. In the present study, we investigated the altered expression of Ca²⁺-controlled proteins in KA-treated hippocampus. Mice were sacrificed at 24 h after KA (20 mg/kg) systemic injection. We conducted Electroencephalographic (EEG) recording and examined hippocampal alterations by Western blotting and immunostaining in control mice or KA-treated mice. EEG tests showed that KA-treated mice increased seizure frequency and severity compared with control mice during KA-induced seizures. We found that KA decreases hippocalcin and calpain-mediated proteolysis in the hippocampus. In particular, the phosphorylation of Lyn and Btk was increased in KA-treated hippocampus compared to those of control mice. Our findings identify tyrosine kinases such as Lyn/Btk as a critical regulator of Ca²⁺-mediated neurotoxicity in KA-induced seizures.