Behavioural NeuroscienceResearch PaperHistone deactylase inhibition combined with behavioral therapy enhances learning and memory following traumatic brain injury
Section snippets
Animals
All manipulations of animals conformed with the guidelines outlined by the National Institutes of Health in Guide for the Care and Use of Laboratory Animals. Male C57 mice (∼25 g) were purchased from Charles River Laboratories (Wilmington, MA, USA). Mice were group housed and maintained on a 12-h light/dark cycle with ad libitum access to food and water.
Controlled cortical impact injury and drug administration
Animals were initially anesthetized with 5% isoflurane and 2:1 mixture of N2O/O2. While being maintained under anesthesia (2% isoflurane and
Sodium butyrate increases hippocampal histone acetylation
In order to examine if the HDAC inhibitor sodium butyrate can effectively increase hippocampal histone acetylation, mice (n=4/condition) were injected i.p. with (1.2 g/kg) of sodium butyrate or an equal volume of vehicle. This dose has been previously used to examine the effect of this compound on memory formation (Fischer et al., 2007). Thirty minutes following injection, hippocampal tissues were dissected and processed for Western analysis. Fig. 1 shows pictures of representative Western
Discussion
Memory functions, especially hippocampus-dependent learning and memory, are often impaired after TBI. These dysfunctions are thought to be due, in part, to both neuronal death and impaired plasticity of the surviving neurons (Lyeth et al 1990, Zhang et al 2005). Epigenetic changes, such as histone acetylation and methylation, regulate chromatin remodeling and are therefore important contributors to the gene regulation involved in neural development and plasticity. When acetylated, histones
Acknowledgments
The authors would like to thank Jing Zhao, Hyung Jin Ahn, and Min Zhang for technical assistance in performing the cortical impact injury and behavioral studies. This work was supported, in part, by grants from the NIH (NS049160, NS053588, MH072933).
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