Neuroprotective effects of FK506 against excitotoxicity in organotypic hippocampal slice culture.
FK506 has been originally classified as an immunosuppressant and is known to exhibit neurotrophic actions in vitro and protective effects on some neurological conditions. We investigated the neuroprotective effects of FK506 on kainic acid (KA)-induced neuronal death in organotypic hippocampal slice cultures (OHSCs). After an 18 h KA (5 microM) treatment, significantly neuronal death was detected in the CA3 region using propidium iodide staining. However, neuronal death was significantly prevented at 24 and 48 h after treatment with 0.1 microM FK506. Using cresyl violet staining, we also observed that an increased number of CA3 neurons survived in the 0.1 microM FK506 group compared to the KA only group. Based on the results of the Western blot analysis, the expressions of 5-lipoxygenase and caspase-3 were reduced 24h after 0.1 microM FK506 treatment. The levels of superoxide dismutase (SOD) and phospho-Akt expression were increased by treatment with 0.1 microM FK506. These results suggest that FK506 may have a positive role in protecting neurons against cell death in the KA injury model of OHSCs.
Lee
Kyung Hee
KH
Department of Dental Hygiene, Division of Health Science, Dongseo University, Busan, Republic of Korea.
Won
Ran
R
Department of Biomedical Laboratory Science, Division of Health Science, Dongseo University, Busan, Republic of Korea.
Kim
Un Jeng
UJ
Department of Physiology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
Kim
Ga Min
GM
Department of Physiology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.
Chung
Myung-Ae
MA
Electronics and Telecommunications Research Institute, Daejeon, Republic of Korea.
Sohn
Jin-Hun
JH
Department of Psychology, Chungnam National University, Daejeon, Republic of Korea.
Lee
Bae Hwan
BH
Department of Physiology, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: bhlee@yuhs.ac.
D000818:Animals; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects; D007608:Kainic Acid / Q000633:toxicity; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000494:pharmacology*
D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D007608:Kainic Acid; D016559:Tacrolimus