The neuroprotective effect of memantine on methamphetamine-induced cognitive deficits.
Repeated exposure to methamphetamine (METH) can cause severe neurotoxicity to the cortical neurons. In the present study, we investigated the effect of METH on cognitive function deficits, and determined the neuroprotective effects of memantine (MEM) on memory impairment induced by METH. The protein levels of Bcl-2 and cleaved caspase-3 in prefrontal cortex (PFC) were further examined to exploring the underlying mechanism. We found that repeated METH administration impaired long term (24h) memory retention without affecting short term (5min) memory retention. Co-administration of MEM with METH before training session significantly improved METH-induced cognitive function. METH significantly decreased expression level of Bcl-2 and increased expression level of cleaved caspase-3 in the PFC. The changes can be prevented by MEM pretreatment. Thus, these results demonstrated that MEM pretreatment reversed METH-induced changes of protein levels of apoptotic-related gene, and produced protective effects against METH-induced cognitive deficits, suggesting the effectiveness of MEM may be due to its anti-apoptotic activity.
Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica and Collaborative Innovation Center for Brain Science, Chinese Academy of Sciences, Shanghai 201203, China.
Jian-Dong
JD
Long
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
Yao
Y
Liu
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
Dong-Liang
DL
Jiao
Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica and Collaborative Innovation Center for Brain Science, Chinese Academy of Sciences, Shanghai 201203, China.
Yu-Jun
YJ
Wang
Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica and Collaborative Innovation Center for Brain Science, Chinese Academy of Sciences, Shanghai 201203, China.
Gui-Ying
GY
Zan
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
Yun-Yue
YY
Ju
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China. Electronic address: drminzhao@gmail.com.
Min
M
Zhao
Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica and Collaborative Innovation Center for Brain Science, Chinese Academy of Sciences, Shanghai 201203, China.
Jing-Gen
JG
Liu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D008297:Male; D008559:Memantine / Q000008:administration & dosage*; D008568:Memory / Q000187:drug effects*; D057567:Memory, Long-Term / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D008694:Methamphetamine; D053148:Caspase 3; D008559:Memantine
Apoptosis; Cognitive deficits; Memantine; Methamphetamine; Prefrontal cortex