越鞠甘麦大枣汤对产后抑郁小鼠前额叶BDNF-TrkB通路的影响
Effects of Yueju Ganmai Dazao Decoction on BDNF-TrkB Pathway in Prefrontal Lobe of Postpartum Depression Mice
-
摘要: 目的 探讨越鞠甘麦大枣汤(越甘汤)对产后抑郁症(Postpartum depression,PPD)小鼠的快速抗抑郁作用,并从脑源性神经营养因子(BDNF)-酪氨酸蛋白激酶B(TrkB)通路探讨PPD的发病机制及中药起效的作用机制。方法 将40只Balb/c雌性小鼠随机分为2组,空白组不给予任何刺激,孕前应激组给予慢性束缚刺激。3周后将孕前应激组小鼠进行雌雄合笼交配怀孕,分娩后3周检测小鼠的糖水偏好率和强迫游泳不动时间。将孕前应激组诱导建立的PPD小鼠随机分为3组:模型组、越甘汤组和氯胺酮组,检测药物对小鼠的干预作用,并取小鼠前额叶检测BDNF、TrkB、糖原合酶激酶3β(GSK3β)和p-GSK3β蛋白的表达。结果 产后3周,与空白组比较,模型组的糖水偏好率显著降低(P<0.01),强迫游泳不动时间显著延长(P<0.01),前额叶BDNF、TrkB及p-GSK3β/GSK3β的表达均显著下调(P<0.05)。单次给予越甘汤或氯胺酮24 h之后,小鼠的糖水偏好率显著升高(P<0.01),强迫游泳不动时间显著减少(P<0.01),前额叶BDNF、TrkB及p-GSK3β/GSK3β的蛋白表达显著上调(P<0.05)。结论 慢性孕前应激诱导Balb/c小鼠表现出产后抑郁样症状,其发病机制可能与激活其前额叶BDNF-TrkB通路有关。越甘汤对PPD模型小鼠的快速抗抑郁作用可能与改善前额叶BDNF-TrkB信号通路有关。Abstract: OBJECTIVE To study the rapid antidepressant effect of Yueju Ganmai Dazao Decoction (Yuegan Decoction, YG) on postpartum depression (PPD) mice, and to explore the pathogenesis of PPD and the mechanism of Chinese medicine from BDNF-TrkB pathway. METHODS 40 Balb/c female mice were randomly divided into two groups. The control group was not given any stimulation. The pre-pregnancy stressed group was subjected to chronic restraint stress. After 3 weeks, the mice in the pre-pregnancy stress group were mated. The mice were arranged for sucrose preference test (SPT) and forced swim test(FST) 3 weeks after delivery. The PPD mice induced by the pre-pregnancy stress were randomly divided into three groups: model group, YG group and ketamine group. The intervention effect of YG on the mice was detected, and the prefrontal lobes of the mice were taken to detect the expression of BDNF, TrkB, p-GSK3β and GSK3β protein. RESULTS After 3 weeks postpartum, the model mice showed depression-like behaviors. Reduced preference in drinking sucrose solution were found in SPT (P<0.01), and immobility in FST was significantly increased (P<0.01). And the expressions of BDNF, TrkB and p-GSK3β/GSK3β in the prefrontal lobe of the PPD model group were significantly reduced (P<0.05), compared to control group. Acute YG improved performance in the SPT and FST (P<0.01), which was similar to ketamine. A single dose of YG or ketamine normalized BDNF-TrkB signaling in the PPD model mice (P<0.05). CONCLUSION Chronic pre-pregnancy stress induces postpartum depression-like symptoms in Balb/c mice. The pathogenesis may be related to activation of the prefrontal BDNF-TrkB pathway. The rapid antidepressant effect of YG on PPD model mice may be related to the improvement of the prefrontal BDNF-TrkB signaling pathway.
-
Key words:
- postpartum depression /
- Yueju Ganmai Dazao Decoction /
- BDNF /
- TrkB /
- GSK3β
-
[1] KENDLER KS, KESSLER RC, WALTERS EE, et al. Stressful life events, genetic liability, and onset of an episode of major depression in women[J]. Focus, 2010, 8(3): 459-470. [2] 夏宝妹, 张海楼, 陈刚. 产后抑郁小鼠模型的构建及越鞠甘麦大枣汤对其抑郁样行为的影响[J].中国药理学通报,2015, 31(9):1324-1328. [3] 夏宝妹,陈畅,陈刚. 越鞠甘麦大枣汤对产后抑郁小鼠海马AKT/mTOR信号通路的影响[J].中国药理学通报,2016, 32(1):119-122. [4] OPAL MD, KLENOTICH SC, MORAIS M, et al. Serotonin 2C receptor antagonists induce fast-onset antidepressant effects[J]. Mol psychiatry, 2014, 19(10): 1106. [5] AUTRY AE, MONTEGGIA LM. Brain-derived neurotrophic factor and neuropsychiatric disorders[J]. Pharmacol Rev, 2012, 64(2): 238-258. [6] DUMAN RS, AGHAJANIAN GK. Neurobiology of rapid acting antidepressants: Role of BDNF and GSK3β[J]. Neuropsychopharmacology, 2014, 39(1): 233. [7] 邓颖,张春虎,张海男,等.柴胡疏肝散及其拆方对抑郁模型大鼠行为及海马、杏仁核、额叶BDNF及其受体TrkB的影响[J]. 中国中西医结合杂志, 2011, 31(10): 1373-1378. [8] MOREIRA FP, BORGES CJ, WIENER CD, et al. Serum brain-derived neurotrophic factor levels in subjects with major depressive disorder with previous suicide attempt: A population-based study[J]. Psychiatry Res, 2018, 262: 500-504. [9] PHILLIPS C. Brain-derived neurotrophic factor, depression, and physical activity: Making the neuroplastic connection[J]. Neural Plast, 2017:1-17. [10] DWIVEDI Y, MONDAL AC, RIZAVI HS, et al. Suicide brain is associated with decreased expression of neurotrophins[J]. Biological Psychiatry, 2005, 58(4): 315-324. [11] CASTREN E, VOIKAR V, RANTAMAKI T. Role of neurotrophic factors in depression[J]. Curr Opin Pharmacol, 2007, 7(1): 18-21. [12] BASTERZI AD, YAZICI K, ASLAN E, et al. Effects of fluoxetine and venlafaxine on serum brain derived neurotrophic factor levels in depressed patients[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2009, 33(2): 281-285. [13] SHIMIZU E, HASHIMOTO K, OKAMURA N, et al. Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants[J]. Biol Psychiatry, 2003, 54(1): 70-75. [14] LOMMATZSCH M, HORYCH K, ZINGLER C, et al. Maternal serum concentrations of BDNF and depression in the perinatal period[J]. Psychoneuroendocrinology, 2006, 31(3): 388-394. [15] YANG X, SONG SQ, XU Y. Resveratrol ameliorates chronic unpredictable mild stress-induced depression-like behavior: involvement of the HPA axis, inflammatory markers, BDNF, and Wnt/β-catenin pathway in rats[J]. Neuropsychiatr Dis Treat, 2017, 13: 2727.
点击查看大图
计量
- 文章访问数: 431
- HTML全文浏览量: 6
- PDF下载量: 376
- 被引次数: 0