Etidronate rescues cognitive deficits through improving synaptic transmission and suppressing apoptosis in 2-vessel occlusion model rats

This is the peer-reviewed version of the following article: Li, W., Yuan, H., Yu, Y., Cheong, Y.-K., Ren, G. and Yang, Z., ‘Etidronate rescues cognitive deficits through improving synaptic transmission and suppressing apoptosis in 2-vessel occlusion model rats’. Journal of Neurochemistry, Vol 140(3): 476–484, February 2017, which has been published in final form at http://dx.doi.org/10.1111/jnc.13904. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Vascular dementia (VD) 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 VD model. Two weeks later, 2VO model rats were treated with ET (10ml/kg/day i.p.) for one 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 (LTP) was also rescued by ET treatment in 2VO rats. Moreover, the LTP 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 TUNEL-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. This article is protected by copyright. All rights reserved.Peer reviewe