gsk-3β is required for memory reconsolidation in adult braingsk-3β需要在成人大脑记忆重塑.pdfVIP

GSK-3b Is Required for Memory Reconsolidation in Adult Brain Tetsuya Kimura, Shunji Yamashita, Shinobu Nakao, Jung-Mi Park, Miyuki Murayama, Tatsuya Mizoroki, Yuji Yoshiike, Naruhiko Sahara, Akihiko Takashima* Lab for Alzheimer’s Disease, RIKEN Brain Science Institute, Wako, Saitama, Japan Abstract Activation of GSK-3b is presumed to be involved in various neurodegenerative diseases, including Alzheimer’s disease (AD), which is characterized by memory disturbances during early stages of the disease. The normal function of GSK-3b in adult brain is not well understood. Here, we analyzed the ability of heterozygote GSK-3b knockout (GSK+/ 2) mice to form memories. In the Morris water maze (MWM), learning and memory performance of GSK+/ 2 mice was no different from that of wild-type (WT) mice for the first 3 days of training. With continued learning on subsequent days, however, retrograde amnesia was induced in GSK+/ 2 mice, suggesting that GSK+/ 2 mice might be impaired in their ability to form long-term memories. In contextual fear conditioning (CFC), context memory was normally consolidated in GSK+/ 2 mice, but once the original memory was reactivated, they showed reduced freezing, suggesting that GSK+/ 2 mice had impaired memory reconsolidation. Biochemical analysis showed that GSK-3b was activated after memory reactivation in WT mice. Intraperitoneal injection of a GSK-3 inhibitor before memory reactivation impaired memory reconsolidation in WT mice. These results suggest that memory reconsolidation requires activation of GSK-3 b in the adult brain. Citation: Kimura T, Yamashita S, Nakao S, Park J-M, Murayama M, et al. (2008) GSK-3b Is Required for Memory Reconsolidation in Adult Brain. PLoS ONE 3(10): e3540. doi:10.1371/journal.pone.0003540