Histone deacetylase inhibitors improve learning consolidation in young and in KA-induced-neurodegeneration and SAMP-8-mutant mice
Histone deacetylase inhibitors improve learning consolidation in young and in KA-induced-neurodegeneration and SAMP-8-mutant mice
复制标题
DOI：
10.1016/j.mcn.2008.06.009
复制
发表时间：
2008-10-01
影响因子：
3.5
通讯作者：
Carrion, Angel M.
中科院分区：
文献类型：
--
作者：
Fontan-Lozano, Angela;Romero-Granados, Rocio;Carrion, Angel M.
组蛋白脱乙酰酶 (HDAC) 是一种将染色质维持在凝结状态的酶，与转录缺失相关。我们研究了 HDAC 在学习和记忆过程中的作用。眨眼经典条件反射 (EBCC) 和物体识别记忆 (ORM) 都会诱导组蛋白 H3 乙酰化 (Ac-H3) 增加。 HDAC 抑制剂的全身治疗改善了 EBCC 和 ORM 测试中的认知过程。免疫组织化学和基因表达分析表明，HDAC 抑制剂的施用降低了 Ac-H3 的刺激阈值，并且基因表达达到学习和记忆所需的水平。最后，我们评估了全身施用 HDAC 抑制剂对神经退行性和衰老小鼠模型的影响。 HDAC 抑制剂逆转了这些模型中 ORM 的学习和巩固缺陷。这些结果指出 HDAC 抑制剂是用于姑息治疗衰老和神经退行性疾病中的学习和记忆障碍的候选药物。 (c) 2008 年，爱思唯尔公司出版。
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.