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

Abstract

: Kainic acid (KA)-induced neuronal cell death is associated with intracellular Ca 2+ influx. However, it is unknown whether Lyn/Btk pathway is involved in the Ca 2+ mediated neurotoxicity and neuronal death induced by KA. In the present study, we investigated the altered expression of Ca 2+ -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 KAtreated mice. EEG tests showed that KAtreated mice increased seizure frequency and severity compared with control mice during KAinduced 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 Ca 2+ mediated neurotoxicity in KAinduced seizures.