Memantine ameliorates tau protein deposition and secondary damage in the ipsilateral thalamus and sensory decline following focal cortical infarction in rats
Authors: Ye-Qun Guo
Yu-Sheng Zhang
Rong-Rong Liu
Yu-Bin Liang
Jia-Min Xu
Pei-Zhi Zhu
Ping-Ping Song
Yun-Hui Zhu
Journal: Neuroscience Letters (2020)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Ischemic stroke; Memantine; Secondary damage; Tau protein; Thalamus.
Affiliations: Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, Guangzhou 510632, Guangdong, China; Department of Neurology and Stroke Center, Zhuhai Hospital Affiliated with Jinan University, Zhuhai 519000, China; Clinical Neuroscience Institute, Jinan University, Guangzhou 510632, Guangdong, China., General hospital of southern theatre command of PLA, Guangzhou 510000, Guangdong, China., Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, Guangzhou 510632, Guangdong, China; Clinical Neuroscience Institute, Jinan University, Guangzhou 510632, Guangdong, China., Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, Guangzhou 510632, Guangdong, China; Clinical Neuroscience Institute, Jinan University, Guangzhou 510632, Guangdong, China. Electronic address: .

Abstract:  Previous studies have reported that memantine presents evidence of therapeutic benefits in several animal models of ischemic stroke and neurodegenerative diseases. However, the effect of memantine on secondary damage in the ipsilateral thalamus after focal cortical infarction remains undefined. Present study investigated whether memantine has a protective effect on secondary damage in the ipsilateral thalamus after focal cerebral infarction in rats. At 24 h after distal middle cerebral artery occlusion (MCAO), rats in the memantine and vehicle groups were intraperitoneal injected with memantine and isopycnic vehicle, respectively, was once daily administered for consecutive 7 days. Infarct size was evaluated through Nissl staining and sensory decline determined using adhesive removal test. Secondary thalamic damage was assessed using Nissl staining and immunofluorescence 8 days after MCAO. Immunoboltting was used to identify tau and apoptosis-associated proteins in the ipsilateral thalamus after MCAO. Results revealed that memantine ameliorated sensory decline compared to the vehicle controls. Subsequently, tau phosphorylated at threonine 231 (p-tau-231), glycogen synthase kinase3βpY216 (GSK3βpY216) and protein phosphatase 2A (PP2ApY307) were reduced by memantine, causing greater reduction in neuronal loss and inhibition of reactive astrogliosis in the ipsilateral ventroposterior thalamic nucleus (VPN) compared with the vehicle groups. In addition, increase in secondary damage-induced TUNEL-positive cells was blunted by memantine, as demonstrated by the significant reduction in expression of apoptosis-associated proteins. Our results suggest that memantine has a neuro-protective effect on secondary damage in the ipsilateral thalamus following MCAO by inhibiting the activity of GSK3βpY216/PP2ApY307 and down regulating the levels of p-tau-231 protein. 

Retracted: No

PubPeer comments:
 Brought to my attention by a reader. Figure 4A. * Red boxes: In the Tau5 row, the Sham and Vehicle panels appear to show an overlap. * Yellow boxes: In the p-T231 row, the MCAO and Vehicle panels appear to show an overlap ![file] ,