title: Neuroprotective effects of okadaic acid following oxidative injury in organotypic hippocampal slice culture.
abstract: Oxidative stress produces neurotoxicity often related with various CNS disorders. A phosphatase inhibitor enhances the actions of the signaling kinases. Protein kinases mediated-action shows the neural protection in brain injury. Phosphatase inhibitor, okadaic acid (OA), may enhance the protection effect and benefit to improve neuronal plasticity in post-injury. Thus, we investigated that the protein prophatase inhibitor affects neuroprotective signaling and neuroplastic changes in hippocampus after oxidative injury. Electrophysiological and biochemical assays were used to observe changes in synaptic efficacy following electrical and/or pharmacological manipulation of synaptic function. Neuronal cell death, as assessed by propidium iodide (PI) uptake, was reduced by OA treatment (24 and 48 h) compared with KA treatment. The pattern of DCFH-DA fluorescence in hippocampal slices corresponded well with PI uptake. The phospho-AKT/AKT ratio showed that the level of phospho-AKT was significantly increased in the OA-treated group. Furthermore, the OA-treated group exhibited significantly increased expression of SOD2 compared with the KA-only group. Optical imaging revealed that KA treatment tended to delay the latency of electrical stimulation and decrease the amplitude of optical signals of synaptic activity. These results suggest that OA may protect hippocampal neurons against oxidative stress and the survived neurons may functional to synaptic plasticity changes.
authors.affiliation: Department of Physiology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Un Jeng
authors.initials: UJ
authors.lastname: Kim
authors.affiliation: Department of Biomedical Laboratory Science, Division of Health Science, Dongseo University, Busan 617-716, Republic of Korea.
authors.forename: Ran
authors.initials: R
authors.lastname: Won
authors.affiliation: Department of Dental Hygiene, Division of Health Science, Dongseo University, Busan 617-716, Republic of Korea. Electronic address: kyhee@gdsu.dongseo.ac.kr.
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000633:toxicity; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019319:Okadaic Acid / Q000494:pharmacology*; D009924:Organ Culture Techniques; D018384:Oxidative Stress / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D019319:Okadaic Acid; D051057:Proto-Oncogene Proteins c-akt; D007608:Kainic Acid
keywords: Hippocampal slice culture; Okadaic acid; Optical imaging; Oxidative injury; Synaptic plasticity