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Journal of Chinese Integrative Medicine ›› 2008, Vol. 6 ›› Issue (3): 283-288.doi: 10.3736/jcim20080313

• Original Experimental Research • Previous Articles     Next Articles

Effects of Valerian on the level of 5-hydroxytryptamine, cell proliferation and neurons in cerebral hippocampus of rats with depression induced by chronic mild stress

Jiu-yu Tang, Yuan-shan Zeng(), Qiao-ge Chen, Ya-jing Qin, Sui-jun Chen, Zhi-qiang Zhong   

  1. Division of Neuroscience, Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong Province 510080, China
  • Received:2007-07-02 Online:2008-03-20 Published:2008-03-15
  • Contact: YS Zeng

Objective: To explore the effects of Valerian on the level of 5-hydroxytryptamine (5-HT), cell proliferation and neuron number in cerebral hippocampus of rats with depression induced by chronic mild stress.Methods: Seventy rats were divided into 7 groups: normal control, untreated, negative control, positive control, and low-, medium- and high-dose Valerian-treated groups. There were 10 rats in each group. Except for the normal control group, depression was induced in rats by chronic mild stress. The depressive rats in the other six groups were intragastrically administered with sodium carboxymethycellulose, fluoxetine, and low, medium and high-dose Valerian, respectively for 3 weeks. After the treatment, the proliferating cells in the hippocampus were labeled by injecting bromodeoxyuridine (BrdU) in 7 groups. The content of 5-hydroxytryptamine (5-HT) in the hippocampus was detected by high-performance liquid chromatography (HPLC), and the number of hippocampal neurons was counted by morphometry.Results: Compared with the normal control group, the levels of 5-HT in the hippocampus in the low- and medium-dose Valerian-treated groups were increased and recovered to normal level. After the administration of low-dose Valerian for 3 weeks, the number of BrdU positive cells and neurons in the hippocampus of the depressive rats were recovered to the normal status.Conclusion: Minidose Valerian may promote the level of 5-HT and cell proliferation in the hippocampus of the depressive rats, and may play a role in saving injured neurons of the hippocampus.

Key words: Valerian officinalis, depressive disorder, stress, hippocampus, 5-hydroxytryptamine, rats

CLC Number: 

  • R285.5

Table 1

5-HT level, and number of BrdU positive cells and perikaryon in hippocampus in seven groups ($\bar{x}$±s )"

Group n 5-HT (ng/g) Number of BrdU positive cells Perikaryon number
Normal control 10 0.27±0.03 33.0±9.9 1230±60
Untreated 10 0.18±0.03* 18.0±3.4* 1108±34*
Negative control 10 0.21±0.03* 19.2±3.4* 1129±38*
Positive control 10 0.40±0.06*△▲ 35.0±6.3△▲ 1194±48△▲
Low-dose Valerian-treated 10 0.31±0.04△▲□ 32.6±5.4△▲ 1232±47△▲
Medium-dose Valerian-treated 10 0.31±0.04△▲□ 18.4±3.7*□■ 1138±31*□■
High-dose Valerian-treated 10 0.22±0.03*□■ 18.2±2.7*□■ 1105±36*□■

Figure 1

BrdU positive nuclei (arrows) of hippocampal dentate gyrus in 7 groups (Immunohistochemical staining, ×100) A: normal control group; B: negative control group; C: untreated group; D: positive control group; E: low-dose Valerian-treated group; F: medium-dose Valerian-treated group; G: high-dose Valerian-treated group."

Figure 2

Neurons of CA3 area of hippocampus in 7 groups (Neutral red staining, ×400) A: normal control group; B: negative control group; C: untreated group; D: positive control group; E: low-dose Valerian-treated group; F: medium-dose Valerian-treated group; G: high-dose Valerian-treated group."

[1] Murray CJ, Lopez AD . Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study[J]. Lancet, 1997,349(9064):1498-1504
doi: 10.1016/S0140-6736(96)07492-2
[2] Oshima Y, Matsuoka S, Ohizumi Y . Antidepressant principles of Valerian fauriei roots[J]. Chem Pharm Bull (Tokyo), 1995,43(1):169-170
doi: 10.1248/cpb.43.169 pmid: 7895306
[3] Willner P, Muscat R, Papp M . Chronic mild stress-induced anhedonia: a realistic animal model of depression[J]. Neurosci Biobehav Rev, 1992,16(4):525-534
doi: 10.1016/S0149-7634(05)80194-0
[4] Wang ZJ, Lu BX, Ji Z . Effect of fluoxetine pretreatment on the expression of BDNF and bcl-2 in rat hippocampus with cerebral ischemia-reperfusion injury[J]. Zhongguo Wei Qin Xi Shen Jing Wai Ke Za Zhi, 2005,10(9):414-416
王占军, 陆兵勋, 姬仲 . 氟西汀预处理对大鼠脑缺血再灌注海马区BDNF和bcl-2表达的影响[J]. 中国微侵袭神经外科杂志, 2005,10(9):414-416
[5] Kuhn HG, Dickinson-Anson H, Gage FH . Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation[J]. J Neurosci, 1996,16(6):2027-2033
doi: 10.1523/JNEUROSCI.16-06-02027.1996
[6] Malberg JE, Eisch AJ, Nestler EJ , et al. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus[J]. J Neurosci, 2000,20(24):9104-9110
doi: 10.1523/JNEUROSCI.20-24-09104.2000
[7] Benninghoff J, Schmitt A , Mossner R, et al.When cells become depressed: focus on neural stem cells in novel treatment strategies against depression[J]. J Neural Transm, 2002,109(5-6):947-962
doi: 10.1007/s007020200078
[8] Zhang LM, Li YF, Gong ZH . Neurogenesis: a novel strategy for the treatment of depression[J]. Sheng Li Ke Xue Jin Zhan, 2005,36(2):109-112
张黎明, 李云峰, 宫泽辉 . 神经元再生: 抑郁症治疗的新策略[J]. 生理科学进展, 2005,36(2):109-112
[9] Craig RK, Hall L, Edbrooke MR , et al. Partial nucleotide sequence of human calcitonin precursor mRNA identifies flanking cryptic peptides[J]. Nature, 1982,295(5847):345-347
doi: 10.1038/295345a0
[10] Deng QY, Wang WD, Li KZ . Studies on chemical constituents in Valerian roots[J]. Fen Xi Ce Shi Xue Bao, 1995,14(2):16-22
邓芹英, 黄维德, 李考铮 . 缬草根化学成分的研究[J]. 分析测试学报, 1995,14(2):16-22
[11] Brezun JM, Daszuta A . Serotonin may stimulate granule cell proliferation in the adult hippocampus, as observed in rats grafted with foetal raphe neurons[J]. Eur J Neurosci, 2000,12(1):391-396
doi: 10.1046/j.1460-9568.2000.00932.x
[12] Gould E, Tanapat P, Rydel T , et al. Regulation of hippocampal neurogenesis in adulthood[J]. Biol Psychiatry, 2000,48(8):715-720
doi: 10.1016/S0006-3223(00)01021-0 pmid: 11063968
[13] Garcia R . Stress, metaplasticity, and antidepressants[J]. Curr Mol Med, 2002,2(7):629-638
doi: 10.2174/1566524023362023
[14] Sapolsky RM . Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders[J]. Arch Gen Psychiatry, 2000,57(10):925-935
doi: 10.1001/archpsyc.57.10.925
[15] Lucassen PJ, Müller MB, Holsboer F , et al. Hippocampal apoptosis in major depression is a minor event and absent from subareas at risk for glucocorticoid overexposure[J]. Am J Pathol, 2001,158(2):453-468
doi: 10.1016/S0002-9440(10)63988-0
[16] Qie JK, Qu HH, Luan XH . Chemical components of Valeriana and its pharmacological study[J]. Zhongguo Yao Xue Za Zhi, 2002,37(10):729-733
doi: 10.3321/j.issn:1001-2494.2002.10.004
郄建坤, 屈会化, 栾新慧 . 缬草属植物化学成分及药理研究概况[J]. 中国药学杂志, 2002,37(10):729-733
doi: 10.3321/j.issn:1001-2494.2002.10.004
[17] Wang YF, Yan J, Sun SG , et al. Effect of Valerian officinalis var latifolia miq on the expression of c-fos and c-jun in rats with focal cerebral ischemia[J]. Guangxi Yi Ke Da Xue Xue Bao, 2004,21(1):10-12
王云甫, 严洁, 孙圣刚 , 等. 宽叶缬草对大鼠局灶性脑缺血后C-Fos、C-Jun表达的影响[J]. 广西医科大学学报, 2004,21(1):10-12
[18] Wang YF, Yan J, Luo GJ , et al. Effects of Valerian officinalis var latifolia miq in the treatment of cerebral infarction in rats[J]. Zhongguo Kang Fu, 2004,19(3):137-138
doi: 10.3870/j.issn.1001-2001.2004.03.003
王云甫, 严洁, 罗国君 , 等. 宽叶缬草治疗局灶性脑缺血的实验研究[J]. 中国康复, 2004,19(3):137-138
doi: 10.3870/j.issn.1001-2001.2004.03.003
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