Temporal expression of hippocampal lysophosphatidic acid receptors and their roles in kainic acid-induced neurotoxicity
In this investigation, the role of hippocampal lysophosphatidic acid (LPA) receptors in the regulation of kainic acid (KA)-induced neurotoxicity was investigated. KA (0.07 μg) intracerebroventricular (i.c.v.) administration increased hippocampal Lpar1, 2, 3, and 5 mRNA levels. In the immunohistochemical study, alteration of LPA1 or LPA3 immunoreactivity was different depending on the hippocampal regions, such as CA1, CA2, CA3, and dentate gyrus. In addition, the i.c.v. pretreatment with LPA1 and LPA3 antagonists, such as VPC12249 (0.05 μg) and VPC32183 (0.05 μg) attenuated KA-induced neuronal cell death in the hippocampal CA3 region. However, the i.c.v. 18:1 LPA (0.05 μg) pretreatment aggravated KA-induced neuronal cell death in the hippocampal CA3 region. Our results suggest that LPA receptors, such as LPA1 and LPA3 activation might play an important role in the regulation of KA-induced neuronal cell death in the hippocampal CA3 region.