title: Role of the Mitochondrial Calcium Uniporter in Rat Hippocampal Neuronal Death After Pilocarpine-Induced Status Epilepticus.
abstract: The mitochondrial calcium uniporter (MCU) is reportedly involved in oxidative stress, apoptosis, and many neurological diseases. However, the role of the MCU in epilepsy remains unknown. In this study, we found that the MCU inhibitor Ru360 significantly attenuated neuronal death and exerted an anti-apoptotic effect on rat hippocampal neurons after pilocarpine-induced status epilepticus (SE), while the MCU activator spermine increased seizure-induced neuronal death and apoptosis. In addition, Ru360 decreased the level of seizure-induced reactive oxygen species (ROS) in mitochondria isolated from rat hippocampi. Moreover, Ru360 restored the altered mitochondrial membrane potential and cytochrome c (CytC) release in epileptic hippocampi. However, spermine treatment exerted an opposite effect on seizure-induced ROS production and mitochondrial membrane potential alteration and CytC release compared with Ru360 treatment. Altogether, the findings of this study suggest that MCU inhibition exerts a neuroprotective effect on seizure-induced brain injury possibly through the mitochondria/ROS/CytC pathway.
authors.affiliation: Department of Internal Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
authors.forename: Cui
authors.initials: C
authors.lastname: Wang
authors.forename: Nanchang
authors.initials: N
authors.lastname: Xie
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Wang
authors.forename: Yulin
authors.initials: Y
authors.lastname: Li
authors.forename: Xinjie
authors.initials: X
authors.lastname: Ge
authors.forename: Menglu
authors.initials: M
authors.lastname: Wang
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010862:Pilocarpine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017975:Ruthenium Compounds / Q000494:pharmacology; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; C112020:Ru 360; D017975:Ruthenium Compounds; C034703:mitochondrial calcium uniporter; D010862:Pilocarpine