Sharma Mahima, Shetty Mahesh Shivarama, Arumugam Thiruma Valavan, Sajikumar Sreedharan
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore-117 597.
Neurobiology/Aging Program, Life Sciences Institute (LSI), National University of Singapore, Singapore-117 456.
Sci Rep. 2015 Nov 18;5:16616. doi: 10.1038/srep16616.
Aging is associated with impaired plasticity and memory. Altered epigenetic mechanisms are implicated in the impairment of memory with advanced aging. Histone deacetylase 3 (HDAC3) is an important negative regulator of memory. However, the role of HDAC3 in aged neural networks is not well established. Late long-term potentiation (late-LTP), a cellular correlate of memory and its associative mechanisms such as synaptic tagging and capture (STC) were studied in the CA1 area of hippocampal slices from 82-84 week old rats. Our findings demonstrate that aging is associated with deficits in the magnitude of LTP and impaired STC. Inhibition of HDAC3 augments the late-LTP and re-establishes STC. The augmentation of late-LTP and restoration of STC is mediated by the activation of nuclear factor kappa B (NFκB) pathway. We provide evidence for the promotion of associative plasticity in aged neural networks by HDAC3 inhibition and hence propose HDAC3 and NFκB as the possible therapeutic targets for treating age -related cognitive decline.
衰老与可塑性和记忆受损有关。表观遗传机制的改变与衰老导致的记忆损害有关。组蛋白去乙酰化酶3（HDAC3）是记忆的重要负调节因子。然而，HDAC3在衰老神经网络中的作用尚未明确。在82 - 84周龄大鼠海马切片的CA1区研究了晚期长时程增强（late-LTP），这是一种记忆的细胞关联及其关联机制，如突触标记和捕获（STC）。我们的研究结果表明，衰老与LTP幅度的缺陷和STC受损有关。抑制HDAC3可增强晚期LTP并重新建立STC。晚期LTP的增强和STC的恢复是由核因子κB（NFκB）通路的激活介导的。我们提供了证据表明HDAC3抑制可促进衰老神经网络中的关联可塑性，因此提出HDAC3和NFκB作为治疗与年龄相关的认知衰退的可能治疗靶点。
