title: Etidronate rescues cognitive deficits through improving synaptic transmission and suppressing apoptosis in 2-vessel occlusion model rats.
abstract: Vascular dementia is a neurodegenerative disorder caused by the reduction of cerebral blood flow. It shows a progressive cognitive impairment. In our previous study, we found that etidronate (ET) showed neuroprotective effects against glutamate-injured PC12 cells. Thus, in this study, we aimed to observe the effects of ET on learning and memory impairment and the related mechanism in 2-vessel occlusion (2VO) model rats. Rats were administered a permanent bilateral common carotid artery occlusion to induce vascular dementia model. Two weeks later, 2VO model rats were treated with ET (20 mg/kg/day i.p.) for 1 week. Results showed that ET improved the spatial learning and memory function in 2VO rats detected by Morris water maze experiment. A reduced long-term potentiation was also rescued by ET treatment in 2VO rats. Moreover, the long-term potentiation-related proteins, calcium/calmodulin-dependent protein kinase II (CaMKII), NMDAR 2B and PSD95 were up-regulated after treatment with ET. By testing the levels of malondialdehyde and superoxide dismutase in 2VO rats, we discovered that ET lowered oxidative stress. Furthermore, ET displayed a better anti-apoptosis ability through detecting the levels of Bcl-2 and Bax protein and terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells. In conclusion, ET shows neuroprotective effects on 2VO rats through rescuing spatial working memory deficits, and a possible mechanism may be related to the increased synaptic transmission and the inhibition of oxidative stress and apoptosis.
authors.affiliation: School of Medicine, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: School of Medicine, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Yuan
authors.affiliation: School of Medicine, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Science and Technology Research Institute, University of Hertfordshire, Hatfield, Hertfordshire, UK.
authors.forename: Yuen-Ki
authors.initials: YK
authors.lastname: Cheong
authors.affiliation: Science and Technology Research Institute, University of Hertfordshire, Hatfield, Hertfordshire, UK.
authors.forename: Guogang
authors.initials: G
authors.lastname: Ren
authors.affiliation: School of Medicine, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials Ministry of Education, Nankai University, Tianjin, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use; D002561:Cerebrovascular Disorders / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015140:Dementia, Vascular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D012968:Etidronic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
chemical_list: D050071:Bone Density Conservation Agents; D012968:Etidronic Acid
keywords: apoptosis; etidronate; long-term potentiation; synaptic transmission; vascular dementia