Increased vulnerability of hippocampal pyramidal neurons to the toxicity of kainic acid in OASIS-deficient mice

• Published in: Journal of neurochemistry 2009-08, Vol.110 (3), p.956-965
• Main Authors: Chihara, Kazuyasu, Saito, Atsushi, Murakami, Tomohiko, Hino, Shin-ichiro, Aoki, Yuri, Sekiya, Hiroshi, Aikawa, Yuji, Wanaka, Akio, Imaizumi, Kazunori
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Animals; astrocyte; Biochemistry; Biological and medical sciences; Cells, Cultured; chaperone; Cyclic AMP Response Element-Binding Protein - deficiency; Cyclic AMP Response Element-Binding Protein - genetics; Cyclic AMP Response Element-Binding Protein - physiology; endoplasmic reticulum stress; Female; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Injuries of the nervous system and the skull. Diseases due to physical agents; kainic acid; Kainic Acid - toxicity; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Tissue Proteins - deficiency; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Neurology; neuronal cell death; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Organic mental disorders. Neuropsychology; Protein folding; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Pyramidal Cells - drug effects; Pyramidal Cells - metabolism; Pyramidal Cells - pathology; Rodents; Toxicity; Traumas. Diseases due to physical agents
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2009.06188.x

The endoplasmic reticulum (ER) stress response is a defense system for dealing with the accumulation of unfolded proteins in the ER lumen. Old astrocyte specifically induced substance (OASIS) is known to be expressed in astrocytes and involved in the ER stress response; however the function of OASIS in the injured brain has remained unclear. In this study, we examined the roles of OASIS in neuronal degeneration in the hippocampi of mice intraperitoneally injected with kainic acid (KA). OASIS mRNA was strongly induced in response to KA injection, with a similar time course to the induction of ER molecular chaperone immunoglobulin heavy chain binding protein mRNA. In situ hybridization showed that KA injection causes induction of immunoglobulin heavy chain binding protein mRNA in glial fibrillary acidic protein-positive astrocytes as well as in pyramidal neurons, although up-regulation of OASIS mRNA was only detected in glial fibrillary acidic protein-positive astrocytes. Primary cultured astrocytes, but not the neurons of OASIS-/- mice, revealed reduced vulnerability to ER stress. Furthermore, pyramidal neurons in the hippocampi of OASIS-/- mice were more susceptible to the toxicity induced by KA than those of wild-type mice. Taken together, these data suggest that OASIS expressed in astrocytes plays important roles in protection against the neuronal damage induced by KA.