Li Junling, Zhang Yan, Li Te, Nie Binbin, Qi Fang, Chen Qijun, Chen Tianxing, Liu Yuhang, Li Gaifen, Li Yubo
School of Traditional Chinese Medicine, Capital Medical University, Beijing, China.
Department of Traditional Chinese Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Front Pharmacol. 2024 Jul 29;15:1383624. doi: 10.3389/fphar.2024.1383624. eCollection 2024.
An accumulating body of research indicates that the pons is related to the occurrence of depression. Si-Ni-San (SNS) is a well-known Chinese herbal formula that is used to treat depression. Chinese herbal formulae have multiple therapeutic characteristics. Although it has been proven that SNS can exert antidepressant effects by improving changes in the limbic system, it is currently unclear whether SNS has therapeutic targets in the pons. This study aimed to explore the therapeutic targets of SNS in the pons for depression treatment.
Two experiments were conducted. In Experiment 1, 32 rats were divided into four groups: (1) a Control (C) group that received distilled water as a vehicle; (2) a Model (M) group that received the chronic unpredictable mild stress (CUMS) procedure and was administered distilled water; (3) a Stress + SNS (MS) group that received the CUMS procedure and was administered SNS dissolved in distilled water; and (4) a Stress + Fluoxetine (MF) group that received the CUMS procedure and was administered fluoxetine dissolved in distilled water. The open field test (OFT), the sucrose preference test (SPT), and the novel object recognition test (NOR) were performed to test the antidepressant effects of SNS. High-throughput mRNA sequencing (RNA-seq) was used to explore possible gene targets of SNS in the pons, and quantitative real-time PCR was performed to verify the results. High-performance liquid chromatography was used to detect neurotransmitters. Finally, correlation analyses were conducted between behaviors, genes expression, and neurotransmitters. In Experiment 2, 18 rats were divided into the same three groups as in Experiment 1: (1) C, (2) M, and (3) MS. fMRI was used to confirm whether SNS altered the pons in a rat model of depression.
SNS significantly improved sucrose preference in the SPT and T-T in the NOR compared to the M group ( < 0.05). RNA-seq filtered 49 differentially expressed genes(DEGs) that SNS could reverse in the pons of the CUMS depression model. Real-time PCR detected six genes, including Complexin2 (Cplx2), Serpinf1, Neuregulin1 (Nrg1), Annexin A1 (Anxa1), β-arrestin 1 (Arrb1) and presenilin 1 (Psen1). SNS significantly reversed changes in the expression of Anxa1, Nrg1, and Psen1 caused by CUMS ( < 0.05), which is consistent with the DEGs results. Additionally, SNS significantly reversed norepinephrine (NE) changes in the pons. There were 18 noteworthy correlations between behavior, genes, and neurotransmitters ( < 0.05). fMRI showed that SNS can decrease the amplitude of low-frequency fluctuations (ALFF) in the pons of living depressed rats.
The pons is an important target brain region for SNS to exert its antidepressant effects. SNS may improve pontine NE levels by regulating the Anxa1, Nrg1, and Psen1 genes, thereby exerting antidepressant effects and improving cognitive function.
越来越多的研究表明，脑桥与抑郁症的发生有关。四逆散（SNS）是一种用于治疗抑郁症的著名中药方剂。中药方剂具有多种治疗特性。虽然已经证明SNS可以通过改善边缘系统的变化发挥抗抑郁作用，但目前尚不清楚SNS在脑桥中是否有治疗靶点。本研究旨在探索SNS在脑桥中治疗抑郁症的靶点。
进行了两项实验。在实验1中，32只大鼠分为四组：（1）对照组（C组），给予蒸馏水作为溶剂；（2）模型组（M组），接受慢性不可预测轻度应激（CUMS）程序并给予蒸馏水；（3）应激+SNS组（MS组），接受CUMS程序并给予溶解于蒸馏水中的SNS；（4）应激+氟西汀组（MF组），接受CUMS程序并给予溶解于蒸馏水中的氟西汀。进行旷场试验（OFT）、蔗糖偏好试验（SPT）和新物体识别试验（NOR）以测试SNS的抗抑郁作用。采用高通量mRNA测序（RNA-seq）探索SNS在脑桥中可能的基因靶点，并进行定量实时PCR验证结果。采用高效液相色谱法检测神经递质。最后，对行为、基因表达和神经递质进行相关性分析。在实验2中，1
