Compound danshen tablet ameliorated aβ25-35-induced spatial memory impairment in mice via rescuing imbalance between cytokines and neurotrophins

BMC Complementary and Alternative Medicine

Li-Hong Wan¹  Shi-Kun Miao¹  Li-Ming Zhou¹  Li-Tao Liu²  Wen Wang³  Meng-Qi Zhang³  Yan Teng³ 

[1] Sichuan University “985 project -- Science and technology innovation platform for novel drug development”, Sichuan University, Chengdu, Sichuan 610041, PR China;Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, PR China;Basic Medicine 2009 undergraduate students, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, PR China

关键词: BDNF;    RACK1;    ChAT;    Spatial memory impairment;    Compound danshen tablet;   

Others  :  1220302
DOI  :  10.1186/1472-6882-14-23

 received in 2013-07-18, accepted in 2014-01-08,  发布年份 2014

【 摘 要 】

Background

Compound Danshen Tablet (CDT), a Traditional Chinese Medicine, has recently been reported to improve spatial cognition in a rat model of Alzheimer’s disease. However, in vivo neuroprotective mechanism of the CDT in models of spatial memory impairment is not yet evaluated. The present study is aimed to elucidate the cellular mechanism of CDT on Aβ_25-35-induced cognitive impairment in mice.

Methods

Mice were randomly divided into 5 groups: the control group (sham operated), the Aβ_25-35 treated group, the positive drug group, and large and small dosage of the CDT groups, respectively. CDT was administered at a dose of 0.81 g/kg and 0.405 g/kg for 3 weeks. The mice in the positive drug group were treated with 0.4 mg/kg of Huperzine A, whereas the mice of the control and Aβ_25-35 treated groups were administrated orally with equivalent saline. After 7 days of preventive treatment, mice were subjected to lateral ventricle injection of Aβ_25-35 to establish the mice model of Alzheimer’s disease. Spatial memory impairment was evaluated by Morris water maze test. Choline acetyltransferase (ChAT) contents in hippocampus and cortex were quantified by ELISA. The levels of cytokines, receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in hippocampus were measured by RT-PCR and ELISA.

Results

The results showed that Aβ_25-35 caused spatial memory impairment as demonstrated by performance in the Morris water maze test. CDT was able to confer a significant improvement in spatial memory, and protect mice from Aβ_25-35-induced neurotoxicity. Additionally, CDT also inhibited the increase of TNF-α and IL-6 level, and increased the expression of choline acetyltransferase (ChAT), receptor of activated protein kinase C1 (RACK1) and brain-derived neurotrophic factor (BDNF) in brain as compared to model mice.

Conclusion

These findings strongly implicate that CDT may be a useful treatment against learning and memory deficits in mice by rescuing imbalance between cytokines and neurotrophins.

【 授权许可】

   
2014 Teng et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Palmer AM: Pharmacotherapy for Alzheimer’s disease: progress and prospects. Trends Pharmacol Sci 2002, 23(9):426-433.
• [2]Selkoe DJ: Alzheimer’s disease is a synaptic failure. Science 2002, 298(5594):789-791.
• [3]Kang J, Rivest S: Lipid Metabolism and Neuroinflammation in Alzheimer’s Disease: A Role for Liver X Receptors. Endocr Rev 2012, 33(5):715-746.
• [4]Puli L, Pomeshchik Y, Olas K, Malm T, Koistinaho J, Tanila H: Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer’s disease. J Neuroinflammation 2012, 9:105. BioMed Central Full Text
• [5]Broussard GJ, Mytar J, Li RC, Klapstein GJ: The role of inflammatory processes in Alzheimer’s disease. Inflammopharmacology 2012, 20(3):109-126.
• [6]Peng S, Wuu J, Mufson EJ, Fahnestock M: Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer’s disease. J Neurochem 2005, 93(6):1412-1421.
• [7]Lu P, Mamiya T, Lu LL, Mouri A, Niwa M, Hiramatsu M, Zou LB, Nagai T, Ikejima T, Nabeshima T: Silibinin attenuates amyloid beta(25–35) peptide-induced memory impairments: implication of inducible nitric-oxide synthase and tumor necrosis factor-alpha in mice. J Pharmacol Exp Ther 2009, 331(1):319-326.
• [8]Xiao Q, Wang C, Li J, Hou Q, Li J, Ma J, Wang W, Wang Z: Ginkgolide B protects hippocampal neurons from apoptosis induced by beta-amyloid 25–35 partly via up-regulation of brain-derived neurotrophic factor. Eur J Pharmacol 2010, 647(1–3):48-54.
• [9]Farlow MR, Cummings JL: Effective pharmacologic management of Alzheimer’s disease. Am J Med 2007, 120(5):388-397.
• [10]Danysz W, Parsons CG, Mobius HJ, Stoffler A, Quack G: Neuroprotective and symptomatological action of memantine relevant for Alzheimer’s disease–a unified glutamatergic hypothesis on the mechanism of action. Neurotox Res 2000, 2(2–3):85-97.
• [11]Santos-Neto Dos LL, Vilhena Toledo de MA, Medeiros-Souza P, Souza de GA: The use of herbal medicine in Alzheimer’s disease-a systematic review. Evid Based Complement Alternat Med 2006, 3(4):441-445.
• [12]Iwasaki K, Satoh-Nakagawa T, Maruyama M, Monma Y, Nemoto M, Tomita N, Tanji H, Fujiwara H, Seki T, Fujii M, Arai H, Sasaki H: A randomized, observer-blind, controlled trial of the traditional Chinese medicine Yi-Gan San for improvement of behavioral and psychological symptoms and activities of daily living in dementia patients. J Clin Psychiatry 2005, 66(2):248-252.
• [13]Tohda C, Naito R, Joyashiki E: Kihi-to, a herbal traditional medicine, improves Abeta(25–35)-induced memory impairment and losses of neurites and synapses. BMC Complement Altern Med 2008, 8:49. BioMed Central Full Text
• [14]Qin RA, Yao XX, Huang ZY: Effects of compound danshen tablets on spatial cognition and expression of brain beta-amyloid precursor protein in a rat model of Alzheimer’s disease. J Tradit Chin Med 2012, 32(1):63-66.
• [15]Lee YW, Kim DH, Jeon SJ, Park SJ, Kim JM, Jung JM, Lee HE, Bae SG, Oh HK, Ho Son KH, Ryu JH: Neuroprotective effects of salvianolic acid B on an Aβ25-35 peptide-induced mouse model of Alzheimer’s disease. Eur J Pharmacol 2013, 704(1–3):70-77.
• [16]Yin Y, Huang L, Liu Y, Huang S, Zhuang J, Chen X, Zhang L, Wu H, Shao F, Zhao Z: Effect of tanshinone on the levels of nitric oxide synthase and acetylcholinesterase in the brain of Alzheimer’s disease rat model. Clin Invest Med 2008, 31(5):E248-E257.
• [17]Bai DL, Tang XC, He XC: Huperzine A, a potential therapeutic agent for treatment of Alzheimer’s disease. Curr Med Chem 2000, 7(3):355-374.
• [18]Huang L, Yao X-h, Lin Q, Xiao X-l: The Fingerprint of Compound Danshen Tablet (In Chinese). Research and Practice on Chinese Medicines 2012, 26(4):66-69.
• [19]Giovannelli L, Casamenti F, Scali C, Bartolini L, Pepeu G: Differential effects of amyloid peptides beta-(1–40) and beta-(25–35) injections into the rat nucleus basalis. Neuroscience 1995, 66(4):781-792.
• [20]Diaz A, Limon D, Chávez R, Zenteno E, Guevara J: Aβ25-35 injection into the temporal cortex induces chronic inflammation that contributes to neurodegeneration and spatial memory impairment in rats. J Alzheimers Dis 2012, 30(3):505-522.
• [21]Mori K, Obara Y, Moriya T, Inatomi S, Nakahata N: Effects of Hericium erinaceus on amyloid β(25–35) peptide-induced learning and memory deficits in mice. Biomed Res 2011, 32(1):67-72.
• [22]D'Hooge R, De Deyn PP: Applications of the Morris water maze in the study of learning and memory. Brain Res Brain Res Rev 2001, 36(1):60-90.
• [23]Hasselmo ME: The role of acetylcholine in learning and memory. Current Opinion in Neurobiology 2006, 16(6):710-715.
• [24]Ling FA, Hui DZ, Ji SM: Protective effect of recombinant human somatotropin on amyloid beta-peptide induced learning and memory deficits in mice. Growth Horm IGF Res 2007, 17(4):336-341.
• [25]Schliebs R, Arendt T: The significance of the cholinergic system in the brain during aging and in Alzheimer’s disease. J Neural Transm 2006, 113(11):1625-1644.
• [26]Ballard CG, Greig NH, Guillozet-Bongaarts AL, Enz A, Darvesh S: Cholinesterases: roles in the brain during health and disease. Curr Alzheimer Res 2005, 2(3):307-318.
• [27]Oda Y: Choline acetyltransferase: the structure, distribution and pathologic changes in the central nervous system. Pathol Int 1999, 49(11):921-937.
• [28]Combs CK, Karlo JC, Kao SC, Landreth GE: beta-Amyloid stimulation of microglia and monocytes results in TNFalpha-dependent expression of inducible nitric oxide synthase and neuronal apoptosis. J Neurosci 2001, 21(4):1179-1188.
• [29]Blasko I, Marx F, Steiner E, Hartmann T, Grubeck-Loebenstein B: TNFalpha plus IFNgamma induce the production of Alzheimer beta-amyloid peptides and decrease the secretion of APPs. FASEB J 1999, 13(1):63-68.
• [30]Spooren A, Kolmus K, Laureys G, Clinckers R, De Keyser J, Haegeman G, Gerlo S: Interleukin-6, a mental cytokine. Brain Res Rev 2011, 67(1–2):157-183.
• [31]Uslu S, Akarkarasu ZE, Ozbabalik D, Ozkan S, Colak O, Demirkan ES, Ozkiris A, Demirustu C, Alatas O: Levels of amyloid Beta-42, interleukin-6 and tumor necrosis factor-alpha in Alzheimer’s disease and vascular dementia. Neurochem Res 2012, 37(7):1554-1559.
• [32]Van Eldik LJ, Thompson WL, Ralay Ranaivo H, Behanna HA, Martin Watterson D: Glia proinflammatory cytokine upregulation as a therapeutic target for neurodegenerative diseases: function-based and target-based discovery approaches. Int Rev Neurobiol 2007, 82:277-296.
• [33]Young AM, Campbell EC, Lynch S, Dunn MH, Powis SJ, Suckling J: Regional susceptibility to TNF-α induction of murine brain inflammation via classical IKK/NF-κB signalling. PLoS One 2012, 7(6):e39049.
• [34]Song C, Zhang Y, Dong Y: Acute and subacute IL-1β administrations differentially modulate neuroimmune and neurotrophic systems: possible implications for neuroprotection and neurodegeneration. J Neuroinflammation 2013, 10(59):31-32.
• [35]Ji C, Song C, Zuo P: The mechanism of memory impairment induced by Aβ chronic administration involves imbalance between cytokines and neurotrophins in the rat hippocampus. Curr Alzheimer Res 2011, 8(4):410-420.
• [36]Battaini F, Pascale A: Protein kinase C signal transduction regulation in physiological and pathological aging. Ann N Y Acad Sci 2005, 1057:177-192.
• [37]He DY, Neasta J, Ron D: Epigenetic regulation of BDNF expression via the scaffolding protein RACK1. J Biol Chem 2010, 285(25):19043-19050.