1. Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology
2. Howard Hughes Medical Institute,
3. Riken-MIT Neuroscience Research Center, Vassar Street, Bldg 46, Cambridge 02139, USA
4. Present address: European Neuroscience Institute (ENI), Medical School University Goettingen, Max Planck Society, Grisebach Strasse 5, Goettingen 37077, Germany.

Correspondence to: Andre Fischer^1,2,3,4Li-Huei Tsai^1,2,3 Correspondence and requests for materials should be addressed to L.H.-T. (Email: lhtsai@mit.edu) or A.F. (Email: andre.fischer@mpi-mail.mpg.de).

Abstract

Neurodegenerative diseases of the central nervous system are often associated with impaired learning and memory, eventually leading to dementia. An important aspect in pre-clinical research is the exploration of strategies to re-establish learning ability and access to long-term memories. By using a mouse model that allows temporally and spatially restricted induction of neuronal loss, we show here that environmental enrichment reinstated learning behaviour and re-established access to long-term memories after significant brain atrophy and neuronal loss had already occurred. Environmental enrichment correlated with chromatin modifications (increased histone-tail acetylation). Moreover, increased histone acetylation by inhibitors of histone deacetylases induced sprouting of dendrites, an increased number of synapses, and reinstated learning behaviour and access to long-term memories. These data suggest that inhibition of histone deacetylases might be a suitable therapeutic avenue for neurodegenerative diseases associated with learning and memory impairment, and raises the possibility of recovery of long-term memories in patients with dementia.

1. Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology
2. Howard Hughes Medical Institute,
3. Riken-MIT Neuroscience Research Center, Vassar Street, Bldg 46, Cambridge 02139, USA
4. Present address: European Neuroscience Institute (ENI), Medical School University Goettingen, Max Planck Society, Grisebach Strasse 5, Goettingen 37077, Germany.

Correspondence to: Andre Fischer^1,2,3,4Li-Huei Tsai^1,2,3 Correspondence and requests for materials should be addressed to L.H.-T. (Email: lhtsai@mit.edu) or A.F. (Email: andre.fischer@mpi-mail.mpg.de).

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