Effects of compound Baihe shugan anshen on stucture and expressions of GR, BDNF and NPY on prefrontal cortex-edge structure in anxious depression model rats

Abstract

Abstract:

AIM: To investigate the effects of compound Baihe shugan anshen on anxiety depression model rat prefrontal cortex-edge(hippocampus and amygdala) structure and expression of GR/BDNF/NPY. METHODS: SD rats were randomly divided into 7 groups according to body weight: the anxious depression model group, the positive drug (venlafaxine 6.75 mg/kg) group, the compound Baihe shugan anshen-high, -middle, -low (24.28 g/kg, 12.24 g/kg, 6.12 g/kg) group, the control group and the vehicle group. Chronic restraint stress plus solitary feeding and subcutaneous injection of CORT (30 mg/kg) for 21 d were administered to build the animal model of anxiety depression. At the same time, the positive drug group and compound Baihe shugan anshen group received intragastric administration. The vehicle group received subcutaneous injection of physiological saline plus 5%DMSO. The control group was fed normally. Morphological changes of prefrontal cortex (PFC), hippocampus and amygdala were analyzed by HE staining, and determination of GR, BDNF and NPY by Western blotting. RESULTS: Compared with the blank control group, glial cells were increased while the neurons were decreased; vertebral neurons were physalides, and nucleus were wither in PFC of anxiety-depression rats. Neurons in hippocampal DG and CA3 area were lost, and the nucleus of neurons in CA3 area was deeply stained. The nucleus of amygdala neurons was fuzzy, the cells were scattered, and the number of cells were decreased significantly. The levels of GR, BDNF and NPY in PFC, hippocampus and amygdala were significantly decreased (P<0.05 or P<0.01). Compared with the model group, prefrontal cortex glial cell proliferation was obviously relieved; cells were arranged in order in the Baihe shugan anshen high dose group. Neurons in hippocampus DG and CA3 were increased and CA3 neurons recovered. The damage of neurons in the amygdala was also reduced. The levels of GR, BDNF and NPY in PFC, hippocampus and amygdala were significantly increased (P<0.05 or P<0.01). CONCLUSION: The anti-anxiety and depression effect of Baihe shugan anshen may be related to the cascade of regulation of GR/BDNF/NPY signal to protect the prefrontal-marginal(hippocampus,amygdala) structural injury.

Key words: anxious depression, compound Baihe shugan anshen, pefrontal cortex-limbic stucture, GR, BDNF, NPY

CLC Number:

R285.5

YANG Qin, DU Qing, ZHAO Hongqing, WANG Yuhong, HAN Yuanshan, YANG Hui, MENG Pan. Effects of compound Baihe shugan anshen on stucture and expressions of GR, BDNF and NPY on prefrontal cortex-edge structure in anxious depression model rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(10): 1090-1098.

References

［1］Bet PM, Hugtenburg JG, Penninx BW, et al. Treatment inadequacy in primary and specialized care patients with depressive and/or anxiety disorders［J］. Psychiatry Res, 2013,210(2): 594-600.
［2］Tejeda HA, O'Donnell P. Amygdala inputs to the prefrontal cortex elicit heterosynaptic suppression of hippocampal inputs［J］. J Neurosci, 2014, 34(43): 14365-14374.
［3］孙韵君. CRH-CRHR1/GABA信号通路与抑郁症发病的分子机制［D］.中国科学技术大学,2016.
［4］Zhang K, Yang J, Wang F, et al. Antidepressant-like effects of Xiaochaihutang in a neuroendocrine mouse model of anxiety/depression［J］. J Ethnopharmacol, 2016, 194: 674-683.
［5］Jangra A, Sriram CS, Dwivedi S, et al. Sodium phenylbutyrate and edaravone abrogate chronic restraint stress-induced behavioral deficits: implication of oxido-nitrosative, endoplasmic reticulum stress cascade, and neuroinflammation［J］. Cell Mol Neurobiol, 2016, 37（1）: 1-17.
［6］Li YF, Yan JC, Wang DQ, et al. Magnetic resonance study of the structure and function of the hippocampus and amygdala in patients with depression［J］.Chin Med J(Engl), 2014, 127(20):3610-3615.
［7］夏传余, 徐胜春, 李光武. 人类杏仁核与情感调节的研究进展［J］. 中华解剖与临床杂志, 2016, 21(1):79-81.
［8］Mitra R, Jadhav S, McEwen BS,et al. Stress duration modulates the spatiotemporal patterns of spine formation in the basolateral amygdale［J］. Proc Natl Acad Sci USA, 2005, 102(26):9371-9376.
［9］Cook SC, Wellman CL. Chronic stress alters dendritic morphology in rat medial prefrontal cortex［J］. J Neurobiol, 2004, 60(2):236-248.
［10］Obrien JT. The 'glucocorticoid cascade' hypothesis in man-prolonged stress may cause permanent brain damage［J］. Br J Psychiatry, 1997, 170:199-201.
［11］Rouleau J,Tanigawa G, Szyf M.The mouse DNA methyltransferase 5'-region.A unique housekeeping gene promoter［J］.J Biol Chem,1992,267(11):7368- 7377.
［12］Martinowich K,Hattori D,Wu H,et al.DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation［J］.Science,2003,302(5646):890- 893.
［13］Vásquez CE, Riener R, Reynolds E, et al. NMDA receptor dysregulation in chronic state: a possible mechanism underlying depression with BDNF downregulation［J］. Neurochem Int, 2014, 79:88-97.
［14］Suliman S, Hemmings S M J, Seedat S. Brain-Derived Neurotrophic Factor (BDNF) protein levels in anxiety disorders: systematic review and meta-regression analysis［J］. Front Integr Neurosci, 2013, 7(7):55.
［15］Pandey SC, Zhang H, Roy A, et al. Central and medial amygdaloid brain-derived neurotrophic factor signaling plays a critical role in alcohol-drinking and anxiety-like behaviors［J］. J Neurosci, 2006, 26(32): 8320-8331.
［16］单菲, 槐中美, 杨和增, 等. 围绝经期综合征焦虑抑郁症状与脑源性神经营养因子的关系［J］. 中国性科学, 2013,22 (7): 94-96.
［17］Wu G, Feder A, Wegener G, et al. Central functions of neuropeptide Y in mood and anxiety disorders［J］. Expert Opin Ther Targets, 2011, 15(11) : 1317-1331.
［18］Jiang P, Dang RL, Li HD, et al. The impacts of swimming exercise on hippocampal expression of neurotrophic factors in rats exposed to chronic unpredictable mild stress［J］.Evid Based Complement Alternat Med, 2014, 2014(34):729-827.
［19］Mickey BJ, Zhou Z, Heitzeg MM, et al. Emotion processing, major depression, and functional genetic variation of neuropeptide Y［J］. Arch Gen Psychiatry, 2011, 68(2) :158-166.
［20］Pandey SC,Carr LG,Heilig M,et al.Neuropeptide y and alcoholism:genetic,molecular,and pharmacological evidence［J］.Alcohol Clin Exp Res,2003,27(2):149-154.

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