Mental Health Research Group, Center for Addiction Research, Mitchell Center for Neurodegenerative Diseases, Dept. of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX, USA.
Mental Health Research Group, Center for Addiction Research, Mitchell Center for Neurodegenerative Diseases, Dept. of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX, USA.
Behav Brain Res. 2019 Dec 30;376:112177. doi: 10.1016/j.bbr.2019.112177. Epub 2019 Aug 23.
Novel targets for depression and anxiety disorders are necessary for the development of more effective pharmacotherapeutics. Our previous study found that the retinoic acid (RA) signaling pathway is the signaling pathway most enhanced in the nucleus accumbens (NAc) shell, a region important for depression, anxiety, and addiction. Genetic manipulations of RA signaling in the NAc affecting addiction-related behavior prompted our study of the role of retinoic acid signaling in depression-related and anxiety-related behavior using in vivo RNA interference. Knockdown of the retinoic acid degradation enzyme cytochrome p450 family 26 subfamily b member 1 (Cyp26b1) in the nucleus accumbens shell increased depression-related behavior while decreasing anxiety-like behavior. Knockdown of the retinoic acid binding protein, cellular RA binding protein 2 (Crabp2), also increased depression-related behavior. Knockdown of another RA binding partner fatty acid binding protein 5 (Fabp5), did not alter these behaviors. These results further support the contention that RA signaling in the NAc shell can affect emotional behavior and that targeting some components of this pathway could be a promising avenue for developing novel treatments for depression and anxiety.
需要寻找新的抑郁症和焦虑症靶点，以开发更有效的药物疗法。我们之前的研究发现，视黄酸（RA）信号通路是在伏隔核壳（NAc 壳）中增强最明显的信号通路，该区域对抑郁、焦虑和成瘾很重要。NAc 中 RA 信号的遗传操作会影响与成瘾相关的行为，这促使我们使用体内 RNA 干扰研究 RA 信号在与抑郁相关和与焦虑相关的行为中的作用。在伏隔核壳中敲低视黄酸降解酶细胞色素 p450 家族 26 亚家族 b 成员 1（Cyp26b1）会增加与抑郁相关的行为，同时减少焦虑样行为。视黄酸结合蛋白细胞 RA 结合蛋白 2（Crabp2）的敲低也会增加与抑郁相关的行为。另一种 RA 结合伴侣脂肪酸结合蛋白 5（Fabp5）的敲低则不会改变这些行为。这些结果进一步支持了 RA 信号在 NAc 壳中可以影响情绪行为的观点，并且靶向该通路的某些成分可能是开发治疗抑郁症和焦虑症的新方法的有前途的途径。
