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.
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Columbia Univ, Howard Hughes Med Inst, Ctr Neurobiol & Behav, New York, NY 10032 USAColumbia Univ, Howard Hughes Med Inst, Ctr Neurobiol & Behav, New York, NY 10032 USA
机构:Columbia Univ, Ctr Neurobiol & Behav, Coll Phys & Surg, New York, NY 10032 USA
Alarcón, JM
Malleret, G
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机构:Columbia Univ, Ctr Neurobiol & Behav, Coll Phys & Surg, New York, NY 10032 USA
Malleret, G
Touzani, K
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机构:Columbia Univ, Ctr Neurobiol & Behav, Coll Phys & Surg, New York, NY 10032 USA
Touzani, K
Vronskaya, S
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机构:Columbia Univ, Ctr Neurobiol & Behav, Coll Phys & Surg, New York, NY 10032 USA
Vronskaya, S
Ishii, S
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机构:Columbia Univ, Ctr Neurobiol & Behav, Coll Phys & Surg, New York, NY 10032 USA
Ishii, S
Kandel, ER
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Columbia Univ, Ctr Neurobiol & Behav, Coll Phys & Surg, New York, NY 10032 USAColumbia Univ, Ctr Neurobiol & Behav, Coll Phys & Surg, New York, NY 10032 USA
Kandel, ER
Barco, A
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机构:Columbia Univ, Ctr Neurobiol & Behav, Coll Phys & Surg, New York, NY 10032 USA
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Columbia Univ, Howard Hughes Med Inst, Ctr Neurobiol & Behav, New York, NY 10032 USAColumbia Univ, Howard Hughes Med Inst, Ctr Neurobiol & Behav, New York, NY 10032 USA
机构:Columbia Univ, Ctr Neurobiol & Behav, Coll Phys & Surg, New York, NY 10032 USA
Alarcón, JM
Malleret, G
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机构:Columbia Univ, Ctr Neurobiol & Behav, Coll Phys & Surg, New York, NY 10032 USA
Malleret, G
Touzani, K
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机构:Columbia Univ, Ctr Neurobiol & Behav, Coll Phys & Surg, New York, NY 10032 USA
Touzani, K
Vronskaya, S
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机构:Columbia Univ, Ctr Neurobiol & Behav, Coll Phys & Surg, New York, NY 10032 USA
Vronskaya, S
Ishii, S
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机构:Columbia Univ, Ctr Neurobiol & Behav, Coll Phys & Surg, New York, NY 10032 USA
Ishii, S
Kandel, ER
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Columbia Univ, Ctr Neurobiol & Behav, Coll Phys & Surg, New York, NY 10032 USAColumbia Univ, Ctr Neurobiol & Behav, Coll Phys & Surg, New York, NY 10032 USA
Kandel, ER
Barco, A
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机构:Columbia Univ, Ctr Neurobiol & Behav, Coll Phys & Surg, New York, NY 10032 USA