タケミヤ タカコ   TAKEMIYA TAKAKO
  竹宮 孝子
   所属   医学部 医学科
   職種   准教授
論文種別 総説
言語種別 英語
査読の有無 査読あり
表題 Roles of prostaglandin synthesis in excitotoxic brain diseases.
掲載誌名 正式名:Neurochemistry international
略  称:Neurochem Int
ISSNコード:0197018601970186
掲載区分国外
巻・号・頁 51(2-4),112-20頁
著者・共著者 Takemiya Takako, Matsumura Kiyoshi, Yamagata Kanato
発行年月 2007
概要 Cyclooxygenase (COX) is a rate-limiting enzyme in prostaglandin synthesis. COX consists of two isoforms, constitutive COX-1 and inducible COX-2. We have first found that COX-2 expression in the brain is tightly regulated by neuronal activity under physiological conditions, and electroconvulsive seizure robustly induces COX-2 mRNA in the brain. Our recent in-depth studies reveal COX-2 expression is divided into two phases, early in neurons and late in non-neuronal cells, such as endothelial cells or astrocytes. In this review, we present that early synthesized COX-2 facilitates the recurrence of hippocampal seizures in rapid kindling model, and late induced COX-2 stimulates hippocampal neuron loss after kainic acid treatment. Hence, we consider the potential role of COX-2 inhibitors as a new therapeutic drug for a neuronal loss after seizure or focal cerebral ischemia. The short-term and sub-acute medication of selective COX-2 inhibitors that suppresses an elevation of prostaglandin E(2) (PGE(2)) may be an effective treatment to prevent neuronal loss after onset of neuronal excitatory diseases. This review also discusses a novel role of vascular endothelial cells in brain diseases. We found that these cells produce PGE(2) by synthesizing COX-2 and microsomal prostaglandin E synthase-1 (mPGES-1) in response to excitotoxicity and neuroinflammation. We also show a possible mechanisms of neuronal damage associated with seizure via astrocytes and endothelial cells. Further analysis of the interaction among neurons, astrocytes and endothelial cells may provide a better understanding of the processes of neuropathological disorders, as well as facilitating the development of new treatments.
DOI 10.1016/j.neuint.2007.05.009
PMID 17629358