Neuroprotective Effects of Citidine-5-diphosphocholine on Impaired Spatial Memory in a Rat Model of Cerebrovascular Dementia

作者：Takasaki Kotaro^*; Uchida Kanako; Fujikawa Risako; Nogami Ai; Nakamura Kazuya; Kawasaki Chihiro; Yamaguchi Kazuko; Morita Masahiko; Morishita Koji; Kubota Kaori; Katsurabayashi Shutaro; Mishima Kenichi; Fujiwara Michihiro; Iwasaki Katsunori

来源：Journal of Pharmacological Sciences, 2011, 116(2): 232-237.

DOI：10.1254/jphs.11013FP

• citidine-5-diphosphocholine (CDP-choline)
• spatial memory
• repeated ischemia
• apoptosis

Citidine-5-diphosphocholine or citicoline (CDP-choline) is used as a neuroprotective and memory-enhancing drug in cerebral stroke, Alzheimer's disease, and other neurovascular diseases. Non-clinical studies have demonstrated the neuroprotective effects of CDP-choline in ischemic animal models. However, the relationship between the neuroprotective effect and the memory enhancing effect of CDP-choline is still unknown. No studies have demonstrated the ameliorative effect on impaired spatial memory and the suppressive effect on neuronal cell death of CDP-choline in the same model. In this study, we examined the effect of CDP-choline on impaired spatial memory and hippocampal CA1 neuronal death in rats subjected to repeated cerebral ischemia, and we compared the mechanism of CDP-choline to that of donepezil. Seven days post administration of CDP-choline (100, 300, 1000 mg/kg per day, p.o.) or donepezil increased correct choices and reduced error choices in an eight-arm radial maze task in a dose-dependent manner. Neuronal cell death of caspase-3 protein-positive neurons in the hippocampus were reduced by repeated administration of CDP-choline at the highest dose. These results suggest that CDP-choline has ameliorative effects on the impairment of spatial memory via hippocampal neuronal cell death in a rat model of cerebral ischemia.

• 出版日期2011-6