title: Time-dependent enhancement of hippocampus-dependent memory after treatment with memantine: Implications for enhanced hippocampal adult neurogenesis.
abstract: Adult hippocampal neurogenesis has been suggested to play modulatory roles in learning and memory. Importantly, previous studies have shown that newborn neurons in the adult hippocampus are integrated into the dentate gyrus circuit and are recruited more efficiently into the hippocampal memory trace of mice when they become 3 weeks old. Interestingly, a single high-dose treatment with the N-methyl-d-aspartate receptor antagonist memantine (MEM) has been shown to increase hippocampal neurogenesis dramatically by promoting cell proliferation. In the present study, to understand the impact of increased adult neurogenesis on memory performance, we examined the effects of a single treatment of MEM on hippocampus-dependent memory in mice. Interestingly, mice treated with MEM showed an improvement of hippocampus-dependent spatial and social recognition memories when they were trained and tested at 3-6 weeks, but not at 3 days or 4 months, after treatment with MEM. Importantly, we observed a significant positive correlation between the scores for spatial memory (probe trial in the Morris water maze task) and the number of young mature neurons (3 weeks old) in MEM-treated mice, but not saline-treated mice. We also observed that the young mature neurons generated by treatment with MEM were recruited into the trace of spatial memory similarly to those generated through endogenous neurogenesis. Taken together, our observations suggest that treatment with MEM temporally improves hippocampus-dependent memory formation and that the newborn neurons increased by treatment with MEM contribute to this improvement when they become 3 weeks old.
authors.affiliation: Department of Bioscience, Faculty of Applied Bioscience, Tokyo University of Agriculture, Setagaya-ku, Tokyo, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Ishikawa
authors.forename: Ryang
authors.initials: R
authors.lastname: Kim
authors.forename: Takashi
authors.initials: T
authors.lastname: Namba
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kohsaka
authors.forename: Shigeo
authors.initials: S
authors.lastname: Uchino
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kida
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D016922:Cellular Senescence; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008559:Memantine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D021641:Recognition, Psychology / Q000187:drug effects* / Q000502:physiology; D012919:Social Behavior; D065852:Spatial Memory / Q000187:drug effects* / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D008559:Memantine
keywords: Morris water maze; NMDA receptor; cAMP-responsive element binding protein; dentate gyrus; social recognition