Epigenetic changes associated with aging have been linked to functional and cognitive deficits in the adult CNS. Histone acetylation is involved in the control of the transcription of plasticity and regeneration-associated genes. The intrinsic axon growth capacity in the CNS is negatively regulated by phosphatase and tensin homolog (Pten). Inhibition of Pten is an effective method to stimulate axon growth following an injury to the optic nerve, corticospinal tract (CST), and rubrospinal tract (RST). Our laboratory has previously demonstrated that the deletion of Pten in aged animals diminishes the regenerative capacity in rubrospinal neurons. We hypothesize that changes in the chromatin structure might contribute to this age-associated decline. Here, we assessed whether Trichostatin A (TSA), a histone deacetylases (HDACs) inhibitor, reverses the decline in regeneration in aged Ptenf/f mice. We demonstrate that HDAC inhibition induces changes in the expression of GAP43 in both young and aged Ptenf/f mice. The regenerative capacity of the RST did not improve significantly in young mice, neither their motor function on the horizontal ladder or cylinder test after TSA treatment for 7 days. Interestingly, TSA treatment in the aged mice worsened their motor function deficits, suggesting that the systemic treatment with TSA might have an overall adverse effect on motor recovery after SCI in aged animals.

中文翻译：

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HDAC抑制导致SCI后红核脊髓轴突中PTEN缺失的年龄依赖性相反再生效应。

与衰老相关的表观遗传变化与成人中枢神经系统的功能和认知缺陷有关。组蛋白乙酰化参与控制可塑性和再生相关基因的转录。中枢神经系统内在的轴突生长能力受到磷酸酶和张力蛋白同源物 (Pten) 的负调控。抑制 Pten 是刺激视神经、皮质脊髓束 (CST) 和红核脊髓束 (RST) 损伤后轴突生长的有效方法。我们的实验室先前已经证明，老年动物中 Pten 的缺失会降低红核脊髓神经元的再生能力。我们假设染色质结构的变化可能导致这种与年龄相关的衰退。在这里，我们评估了曲古抑菌素 A (TSA)，一种组蛋白去乙酰化酶 (HDAC) 抑制剂，逆转老年 Ptenf/f 小鼠再生能力的下降。我们证明 HDAC 抑制诱导年轻和老年 Ptenf/f 小鼠中 GAP43 表达的变化。RST 的再生能力在年轻小鼠中没有显着改善，在 TSA 治疗 7 天后，它们在水平阶梯或圆柱体测试中的运动功能也没有改善。有趣的是，老年小鼠的 TSA 治疗加重了它们的运动功能缺陷，这表明用 TSA 全身治疗可能对老年动物 SCI 后的运动恢复产生总体不利影响。在 TSA 治疗 7 天后，他们在水平梯子或圆柱体测试中的运动功能均未出现。有趣的是，老年小鼠的 TSA 治疗加重了它们的运动功能缺陷，这表明用 TSA 全身治疗可能对老年动物 SCI 后的运动恢复产生总体不利影响。在 TSA 治疗 7 天后，他们在水平梯子或圆柱体测试中的运动功能均未出现。有趣的是，老年小鼠的 TSA 治疗加重了它们的运动功能缺陷，这表明用 TSA 全身治疗可能对老年动物 SCI 后的运动恢复产生总体不利影响。