Editors' ChoiceNeuroscience

Regaining the Lost Past

Science's STKE  15 May 2007:
Vol. 2007, Issue 386, pp. tw164
DOI: 10.1126/stke.3862007tw164

People with Alzheimer’s disease or related neurodegenerative disorders may progress from absentmindedness and difficulty learning new things to a heartbreaking state in which they forget their own past and no longer recognize the faces of people they love. Expression of p25 (a truncated form of the p35 regulatory subunit of cyclin-dependent kinase 5) is associated with various neurodegenerative disorders, and the CK-p25 Tg mouse, in which p25 expression--and thereby neuronal loss--can be conditionally regulated, is a model for these disorders. Fischer et al. found that exposing CK-p25 Tg mice to an enriched environment (after neuronal loss had occurred and learning was impaired) improved their associative and spatial learning. Moreover, environmental enrichment led to the recovery of long-term memories that had apparently been lost. Experiments in wild-type mice revealed that exposure to an enriched environment stimulated histone acetylation in the hippocampus and cortex. The histone deacetylase (HDAC) inhibitor sodium butyrate (SB) improved associative and spatial learning in wild-type and CK-p25 Tg mice (after p25 induction) and, like environmental enrichment, enhanced dendritic and synaptic growth in CK-p25 Tg mice without affecting brain atrophy or neuronal loss. Furthermore, SB enabled the recovery of lost memories. The authors conclude that their data raise the possibility that HDAC inhibitors may provide a means to enable people with neurodegenerative disorders associated with memory loss to recover lost memories. Sweatt provides thoughtful commentary, noting (as do the authors) that HDAC inhibitors may affect the acetylation status of proteins other than histones.

A. Fischer, F. Sananbenesi, X. Wang, M. Dobbin, L. H. Tsai, Recovery of learning and memory is associated with chromatin remodelling. Nature 447, 178-182 (2007). [PubMed]

J. D. Sweatt, Down memory lane. Nature 447, 151-152 (2007). [PubMed]