Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
Life Sci. 2019 Oct 15;235:116819. doi: 10.1016/j.lfs.2019.116819. Epub 2019 Aug 29.
Traumatic brain injury (TBI) not only induces physiological disabilities but also leads to cognitive impairment. However, no effective therapeutic approach for TBI-related memory decline exists. In this study, we treated TBI mice with cinnamic acid (CNA) to detect whether CNA is able to rescue the memory deficits induced by TBI and to explore the potential mechanisms.
Mice were divided into the following groups: the sham group, the TBI group, the TBI + CNA group and the CNA group. Basic physiological parameters, neurological severity score and brain water content were analyzed. The Morris water maze and inhibitory avoidance step-down task were used to determine learning and memory. Golgi staining was used to measure alterations in dendritic spines. Western blot analysis and a commercial kit were used to detect the content and activity of HDAC2. qPCR was used to detect the relative level of miR-455.
CNA did not affect physiological function but effectively restored neurological function and brain edema. CNA alleviated the memory impairments induced by TBI in both the Morris water maze and step-down task. CNA also recovered abnormalities in the synapses of TBI mice by suppressing the activity of HDAC2. Furthermore, CNA did not alter HDAC mRNA because it promoted the expression of miR-455-3p, a miRNA that regulates HDAC2 at the posttranscriptional level.
The application of CNA effectively treats TBI-induced memory deficits by increasing miR-455-3p and by inhibiting HDAC2.
创伤性脑损伤（TBI）不仅会导致生理残疾，还会导致认知障碍。然而，目前尚无针对 TBI 相关记忆减退的有效治疗方法。在这项研究中，我们用肉桂酸（CNA）治疗 TBI 小鼠，以检测 CNA 是否能够挽救 TBI 引起的记忆缺陷，并探讨其潜在机制。
将小鼠分为以下几组：假手术组、TBI 组、TBI+CNA 组和 CNA 组。分析基本生理参数、神经严重程度评分和脑水含量。使用 Morris 水迷宫和抑制性避错跳下任务来确定学习和记忆能力。使用 Golgi 染色来测量树突棘的变化。Western blot 分析和商业试剂盒用于检测 HDAC2 的含量和活性。qPCR 用于检测 miR-455 的相对水平。
CNA 不影响生理功能，但能有效恢复神经功能和脑水肿。CNA 缓解了 Morris 水迷宫和避错跳下任务中 TBI 引起的记忆障碍。CNA 还通过抑制 HDAC2 的活性，恢复了 TBI 小鼠突触的异常。此外，CNA 没有改变 HDAC mRNA，因为它促进了 miR-455-3p 的表达，miR-455-3p 是一种在转录后水平调节 HDAC2 的 miRNA。
CNA 的应用通过增加 miR-455-3p 并抑制 HDAC2，有效地治疗了 TBI 引起的记忆缺陷。
