Frontiers in Molecular Neuroscience (Sep 2015)

Suberoylanilide Hydroxamic Acid, A Histone Deacetylase Inhibitor, Attenuates Postoperative Cognitive Dysfunction in Aging Mice

  • Min eJia,
  • Wen-Xue eLiu,
  • He-Liang eSun,
  • Yan-Qing eChang,
  • Jiao-Jiao eYang,
  • Mu-Huo eJi,
  • Jian-Jun eYang,
  • Chen-Zhuo eFeng

DOI
https://doi.org/10.3389/fnmol.2015.00052
Journal volume & issue
Vol. 8

Abstract

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Postoperative cognitive dysfunction (POCD) is a recognized clinical entity characterized with cognitive deficits after anesthesia and surgery, especially in aged patients. Previous studies have shown that histone acetylation plays a key role in hippocampal synaptic plasticity and memory formation. However, its role in POCD remains to be determined. Here, we show that suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, attenuates POCD in aging Mice. After exposed to the laparotomy, a surgical procedure involving an incision into abdominal walls to examine the abdominal organs, 16- but not 3-month old male C57BL/6 mice developed obvious cognitive impairments in the test of long-term contextual fear conditioning. Intracerebroventricular (i.c.v.) injection of SAHA at the dose of (20 μg/2 μl) 3 hours before and daily after the laparotomy restored the laparotomy-induced reduction of hippocampal acetyl-H3 and acetyl-H4 levels and significantly attenuated the hippocampus-dependent long-term memory impairments in 16-month old mice. SAHA also reduced the expression of cleaved caspase-3, inducible nitric oxide synthase and N-methyl-D-aspartate receptor-calcium/calmodulin dependent kinase II pathway, and increased the expression of brain-derived neurotrophic factor, synapsin 1, and postsynaptic density 95. Taken together, our data suggest that the decrease of histone acetylation contributes to POCD and may serve as a target to improve the neurological outcome of POCD.

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