Histone deacetylase inhibitors improve learning consolidation in young and in KA-induced-neurodegeneration and SAMP-8-mutant mice

被引:86
作者
Fontan-Lozano, Angela [1 ]
Romero-Granados, Rocio [1 ]
Troncoso, Julieta [1 ,2 ]
Munera, Alejandro [1 ,3 ]
Delgado-Garcia, Jose Maria [1 ]
Carrion, Angel M. [1 ]
机构
[1] Univ Pablo Olavide Sevilla, Div Neurociencias, Seville 41013, Spain
[2] Univ Nacl Colombia, Dept Biol, Fac Ciencias, Bogota, DC, Colombia
[3] Univ Nacl Colombia, Dept Ciencias Fisiol, Fac Med, Bogota, DC, Colombia
关键词
Learning; Consolidation; Histone H3 acerylation; Sodium butyrate; Trichostatin A; Histone deacetylase; Gene expression; SAMP-8; mice; Kainic acid; Aging;
D O I
10.1016/j.mcn.2008.06.009
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Histone deacetylases (HDAC) are enzymes that maintain chromatin in a condensate state, related with absence of transcription. We have studied the role of HDAC on learning and memory processes. Both eyeblink classical conditioning (EBCC) and object recognition memory (ORM) induced an increase in histone H3 acetylation (Ac-H3). Systemic treatment with HDAC inhibitors improved cognitive processes in EBCC and in ORM tests. Immunohistochemistry and gene expression analyses indicated that administration of HDAC inhibitors decreased the stimulation threshold for Ac-H3, and gene expression to reach the levels required for learning and memory. Finally, we evaluated the effect of systemic administration of HDAC inhibitors to mice models of neurodegeneration and aging. HDAC inhibitors reversed learning and consolidation deficits in ORM in these models. These results point Out HDAC inhibitors as candidate agents for the palliative treatment of learning and memory impairments in aging and in neurodegenerative disorders. (c) 2008 Published by Elsevier Inc.
引用
收藏
页码:193 / 201
页数:9
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