Etidronate–zinc Complex Ameliorated Cognitive and Synaptic Plasticity Impairments in 2-Vessel Occlusion Model Rats by Reducing Neuroinflammation

In this study, the novel drug etidronate–zinc complex (Eti–Zn) was used to detect its role in synaptic plasticity and learning and memory functions in a rat model of 2-VO. Chronic cerebral hypoperfusion was induced by permanent occlusion of the common carotid artery bilaterally in adult Sprague–Dawley rats. Eti–Zn (20 mg/kg/day, tail vein injection) was administered for 7 days after a two-week operation. After treatment, a series of tests were carried out. Here, we found that Eti–Zn could reduce spatial learning and memory impairments in 2-VO model rats via the Morris water maze test. We also found that animals treated with Eti–Zn showed preference for the new-object in the novel object recognition test. In addition, the long-term potentiation and depotentiation from the Schaffer collaterals to the CA1 region in the hippocampus were enhanced by Eti–Zn treatment in 2-VO model rats. Furthermore, Eti–Zn significantly up-regulated NMDA receptor (NR) 2A, NR2B, postsynaptic density protein 95 and synaptophysin levels and prevented the destruction of dendritic spines. Moreover, Eti–Zn treatment reduced both the over-activation of microglia and the expressions of neuroinflammatory cytokines (TNF-α, IL-1β and IL-6) in the hippocampus. The increased NF-κB signaling pathway in the hippocampus of 2-VO rats was reversed after Eti–Zn treatment. In summary, these findings suggest that Eti–Zn could ameliorate the synaptic plasticity and cognitive impairments by r...
Source: Neuroscience - Category: Neuroscience Source Type: research