Cinnamic acid rescues behavioral deficits in a mouse model of traumatic brain injury by targeting miR-455-3p/HDAC2

• Published in: Life sciences (1973) 2019-10, Vol.235, p.116819, Article 116819
• Main Authors: Guo, Shewei, Zhen, Yingwei, Zhu, Zhiqiang, Zhou, Guosheng, Zheng, Xiangyu
• Format: Article
• Language: English
• Subjects: Abnormalities; Animal memory; Animals; Behavior, Animal - drug effects; Brain; Brain Injuries, Traumatic - complications; Cinnamates - pharmacology; Cinnamic acid; Cognitive ability; Dendritic spines; Disabilities; Edema; Gene expression; HDAC2; HDAC2 protein; Head injuries; Histone deacetylase; Histone Deacetylase 2 - genetics; Histone Deacetylase 2 - metabolism; Male; Maze Learning; Memory; Memory Disorders - etiology; Memory Disorders - metabolism; Memory Disorders - prevention & control; Memory impairments; Mice; Mice, Inbred C57BL; MicroRNAs - genetics; miRNA; Moisture content; mRNA; Physiology; Post-transcription; Synapses; Synaptic Transmission - drug effects; TBI; Traumatic brain injury; Water content
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2019.116819

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. [Display omitted]