The c-Jun N-terminal kinase inhibitor SP600125 is neuroprotective in amygdala kindled rats.
c-Jun N-terminal kinase (JNK) is implicated in cell death in neurodegenerative disorders and has been taken as a critical point between the physiological and pathological status. JNK specific inhibitor SP600125 has been found to have a protective effect against transient brain ischemia/reperfusion-induced neuronal death in rat hippocampal CA1 region. Former studies have shown the relation between JNK phosphorylation and neuronal damage in models of brain ischemia or in chemically or acute electrically kindled animal in which the stimulus-induced JNK phosphorylation was temporary or transient. In this study, the effect of repeated activation of JNK was examined in the amygdala kindled rats, under or without intraventrical infusion of SP600125, compared with the sham control. JNK phosphorylation was detected by Western blot and immunofluorescent staining in hippocampal extracts and in slices respectively. Nissl staining was performed to detect the neuronal defect. We found that the level of JNK phosphorylation (46KD) in the hippocampus increased in the amygdala kindled rats, whereas such JNK phosphorylation could be inhibited by SP600125. Expression of total JNK in the hippocampus remained unchanged in kindled rats compared with the sham control, and was not affected by SP600125. Neuronal defect was marked in the kindling group and in the vehicle DMSO group, and was alleviated under the administration of SP600125. These findings suggest that JNK phosphorylation is involved in the process of hippocampal sclerosis in the mesial temporal lobe epilepsy (TLE). JNK signaling pathway may be a new target to interfere with the development of hippocampal sclerosis in the temporal lobe epilepsy. The JNK inhibitor SP600125 can show a protective effect on hippocampal neurons in TLE by inhibiting JNK activation.
Chen
Xu
X
Department of Neurosurgery, Tongji Hospital, Huazhong University of Science and Technology, Jiefang Ave 1095, 430030 Wuhan, China.
Wu
Jun
J
Hua
Dong
D
Shu
Kai
K
Wang
Jian-Zhi
JZ
Li
Ling
L
Lei
Ting
T
D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D015153:Blotting, Western; D004567:Electrodes, Implanted; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000873:Anthracenes; D018696:Neuroprotective Agents; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases