differential effects of single or repeated restraint stress on kainic acid-induced neuronal death in the hippocampal CA3 region: the role of glucocorticoid and various signal molecules

• Published in: Journal of neurochemistry Vol. 103; no. 4; pp. 1530 - 1541
• Main Authors: Kwon, Min-Soo, Seo, Young-Jun, Choi, Seung-Min, Choi, Hee-Woo, Jung, Jun-Sub, Park, Soo-Hyun, Suh, Hong-Won
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.11.2007; Blackwell Publishing Ltd; Blackwell
• Subjects: Ageing, cell death; Animals; Binding sites; Biochemistry; Biological and medical sciences; Cell Death; Cell Death - drug effects; Cell Death - physiology; Cell physiology; Dose-Response Relationship, Drug; drug effects; Fundamental and applied biological sciences. Psychology; Glucocorticoids; Glucocorticoids - physiology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Kainic Acid; Kainic Acid - toxicity; Male; Medical sciences; metabolism; methods; Mice; Mice, Inbred ICR; Molecular and cellular biology; Nervous system (semeiology, syndromes); Neurology; neuronal death; Neurons; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; pathology; phosphorylated calcium/calmodulin dependent protein kinase II; phosphorylated cyclic-AMP response element binding protein; physiology; Proteins; Restraint, Physical; Restraint, Physical - methods; Signal Transduction; Signal Transduction - drug effects; Signal Transduction - physiology; Stress; Stress, Physiological; Stress, Physiological - metabolism; Stress, Physiological - pathology; Time Factors; toxicity; Phosphorylation; kainic acid; Toxicity; Central nervous system; Glucocorticoid; Stress; Encephalon; Treatment; Cell death; neuronal death; Glucocorticoid receptor; Serum; Antagonist; Transcription factor CREB; Hippocampus; phosphorylated cyclic-AMP response element binding protein; Biological receptor; phosphorylated calcium/calmodulin dependent protein kinase II
• ISSN: 0022-3042; 1471-4159; 1471-4159
• DOI: 10.1111/j.1471-4159.2007.04865.x

The effect of stress mediators following the stress period and addition time is a controversial issue until now. Thus, we aim to clarify the differential effects of single restraint stress (SS) or repeated restraint stress (RS) on kainic acid (KA)-induced neuronal death especially as addressing not only the role of glucocorticoid (Gc) and its receptor but also the signal pathway leading to cAMP response element binding protein phosphorylation (pCREB) and its functional role during stress. In the present study, we found that although RS did not show any difference on serum Gc level and hippocampal Gc receptor level compared to SS, SS exacerbated KA-induced neuronal death in hippocampal CA3 region, but RS did not. Moreover, pre-treatment with RU 38486 (Gc receptor antagonist) abolished the effect of SS on KA-induced neuronal death without an effect on KA toxicity itself. Furthermore, RS aggravates KA-induced neuronal death when CREB phosphorylation was deprived by KN-93 (calcium/calmodulin-dependent protein kinase II inhibitor). However, other signal molecules inhibitors such as PD98059 (MEK1/2 inhibitor) and SP600125 (p-p38 inhibitor) have no effect on KA-induced neuronal death after RS although these signal molecule were increased during SS or RS. These findings suggest that pCREB expression via calcium/calmodulin-dependent protein kinase II phosphorylation during RS comprise one of the balancers against Gc induced by stress.