TY - JOUR
T1 - Etidronate–zinc Complex Ameliorated Cognitive and Synaptic Plasticity Impairments in 2-Vessel Occlusion Model Rats by Reducing Neuroinflammation
AU - Feng, Lina
AU - Gao, Jing
AU - Wang, Yuexiang
AU - Cheong, Yuen Ki
AU - Ren, Guogang
AU - Yang, Zhuo
PY - 2018/10/15
Y1 - 2018/10/15
N2 - 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 (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 reducing neuroinflammation in 2-VO model rats.
AB - 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 (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 reducing neuroinflammation in 2-VO model rats.
KW - chronic cerebral hypoperfusion
KW - etidronate–zinc complex
KW - learning and memory
KW - neuroinflammation
KW - synaptic plasticity
UR - http://www.scopus.com/inward/record.url?scp=85053070928&partnerID=8YFLogxK
U2 - 10.1016/j.neuroscience.2018.08.022
DO - 10.1016/j.neuroscience.2018.08.022
M3 - Article
AN - SCOPUS:85053070928
SN - 0306-4522
VL - 390
SP - 206
EP - 217
JO - Neuroscience
JF - Neuroscience
ER -