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- Title
Iptakalim Alleviates Rotenone-Induced Degeneration of Dopaminergic Neurons through Inhibiting Microglia-Mediated Neuroinflammation.
- Authors
Fang Zhou; Jia-Yong Wu; Xiu-Lan Sun; Hong-Hong Yao; Jian-Hua Ding; Hu, Gang
- Abstract
Inhibition of microglia-mediated neuroinflammation has been regarded as a prospective strategy for treating neurodegenerative disorders, such as Parkinson's disease (PD). In the present study, we demonstrated that systematic administration with iptakalim (IPT), an adenosine triphosphate (ATP)-sensitive potassium channel (KATP) opener, could alleviate rotenone-induced degeneration of dopaminergic neurons in rat substantia nigra along with the downregulation of microglial activation and mRNA levels of tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2). In rat primary cultured microglia, pretreatment with IPT suppressed rotenone-induced microglial activation evidenced by inhibition of microglial amoeboid morphological alteration, declined expression of ED1 (a marker for activated microglia), and decreased production of TNF-α and prostaglandin E2 (PGE2). These inhibitory effects of IPT could be reversed by selective mitochondrial KATP (mitoKATP) channel blocker 5-hydroxydecanoate (5-HD). Furthermore, pretreatment with IPT prevented rotenone-induced mitochondrial membrane potential loss and p38/c-jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) activation in microglia, which might in turn regulate microglial activation and subsequent production of TNF-α and PGE2. These data strongly suggest that the KATP opener IPT may be a novel and promising neuroprotective drug via inhibiting microglia-mediated neuroinflammation.Neuropsychopharmacology (2007) 32, 2570–2580; doi:10.1038/sj.npp.1301381; published online 14 March 2007
- Publication
Neuropsychopharmacology, 2007, Vol 32, Issue 12, p2570
- ISSN
0893-133X
- Publication type
Academic Journal
- DOI
10.1038/sj.npp.1301381