Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10144112 | Neuroscience | 2018 | 27 Pages |
Abstract
As one of the bisphosphonate derivatives, etidronate has proved to be beneficial to spatial learning and memory deficits caused by two-vessel occlusion (2-VO). 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 (20â¯mg/kg/day, tail vein injection) was administered for 7â¯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 reducing neuroinflammation in 2-VO model rats.
Keywords
IL-1βIBA1fEPSP2-VOBPSDepotentiationNR2BNR2ASYPCCHDEPNF-κBTBSCOX-2EtidronateLFSiNOSinitial trainingETINeuroinflammationtwo-vessel occlusionInterleukin-1βBisphosphonateslow-frequency stimulationtheta burst stimulationnovel object recognition testMorris water maze testlong-term potentiationLTPSETtumor necrosis factor-αRETinducible nitric oxide synthaseSynaptophysinCyclooxygenase-2TNF-αnuclear factor-κBionized calcium-binding adaptor molecule 1Chronic cerebral hypoperfusionField excitatory postsynaptic potentialpostsynaptic density protein 95Synaptic plasticityLearning and memory
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Authors
Lina Feng, Jing Gao, Yuexiang Wang, Yuen-Ki Cheong, Guogang Ren, Zhuo Yang,