Effects of Kaixinjieyu, a Chinese herbal medicine preparation, on neurovascular unit dysfunction in rats with vascular depression

BMC Complementary and Alternative Medicine

Qihua Liu²  Hanming Cui²  Jun Zheng²  Duojiao Li²  Wen Chen²  Ying Zhang²  Yanyun Wang²  Shijing Huang²  Jialong Wang²  Xiaoming Lei¹  Juhua Pan² 

[1] Huangpi District Hospital of Traditional Chinese Medicine, Wuhan 430300, Hubei, China;Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China

关键词: Neurogenesis;    Blood–brain barrier;    Neurovascular unit;    Vascular depression;    Chinese herbal medicine;    Kaixinjieyu;   

Others  :  1222525
DOI  :  10.1186/s12906-015-0808-z

 received in 2015-02-16, accepted in 2015-08-07,  发布年份 2015

【 摘 要 】

Background

Kaixinjieyu (KJ), derived from Kaixin and Sini powder, is an effective Chinese herbal medicine preparation used in the treatment of vascular depression (VD). We hypothesize that broad antidepressant effect of KJ results from the improved neurovascular unit (NVU) function via neurogenesis, permeability of blood–brain barrier (BBB) and balance of the fibrinolytic system.

Methods

A VD model of rat was established by chronic unpredictable mild stress and separation after ligation of the bilateral common carotid arteries. The rats were treated with KJ and fluoxetine hydrochloride (FLU) for 21 days, respectively. The behavior and cerebral perfusion were investigated and then NVU functions including neurogenesis, permeability of BBB and balance of the fibrinolytic system were studied using a number of biomarkers and TUNEL assay.

Results

KJ significantly increased sucrose preference, moving distance, number of rearing and cortical blood flow. NVU functions measured by brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB) and tissue plasminogen activator (t-PA) proteins and mRNA, zona occludens protein-1 (ZO-1), occludin and claudin-5 proteins increased significantly, whereas, plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-2 (MMP-2) proteins, mRNA and apoptotic rates of neurons decreased significantly with treatment of KJ. FLU has a function similar to KJ in behavior, regulation of BDNF, TrkB, MMP-2, occludin and apoptotic rates of cells.

Conclusions

KJ has function of reducing depression-like behavior and improving cerebral hypoperfusion, which might be mediated by the up-regulation of neurogenesis and tight junction of BBB, and balance of the fibrinolytic system. The results imply that KJ is better than FLU in improving cerebral hypoperfusion and the fibrinolytic system.

【 授权许可】

   
2015 Pan et al.

【 图 表 】

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【 参考文献 】

• [1]Taylor WD, Aizenstein HJ, Alexopoulos GS. The vascular depression hypothesis: mechanisms linking vascular disease with depression. Mol Psychiatry. 2013; 18(9):963-974.
• [2]Sneed JR, Rindskopf D, Steffens DC, Krishnan KR, Roose SP. The vascular depression subtype: evidence of internal validity. Biol Psychiatry. 2008; 64(6):491-497.
• [3]Gonzalez HM, Tarraf W, Whitfield K, Gallo JJ. Vascular depression prevalence and epidemiology in the United States. J Psychiatr Res. 2012; 46(4):456-461.
• [4]Culang-Reinlieb ME, Johnert LC, Brickman AM, Steffens DC, Garcon E, Sneed JR. MRI-defined vascular depression: a review of the construct. Int J Geriatr Psychiatry. 2011; 26(11):1101-1108.
• [5]Sneed JR, Culang-Reinlieb ME. The vascular depression hypothesis: an update. Am J Geriatr Psychiatry. 2011; 19(2):99-103.
• [6]van Praag HM. Can stress cause depression? World J Biol Psychiatry. 2005; 6 Suppl 2:5-22.
• [7]Bella R, Ferri R, Cantone M, Pennisi M, Lanza G, Malaguarnera G, Spampinato C, Giordano D, Raggi A, Pennisi G. Motor cortex excitability in vascular depression. Int J Psychophysiol. 2011; 82(3):248-253.
• [8]Brunoni AR, Bensenor IM, Alves TC. Therapeutic interventions for vascular depression: a systematic review. Rev Bras Psiquiatr. 2011; 33(4):400-409.
• [9]Iosifescu DV, Renshaw PF, Lyoo IK, Lee HK, Perlis RH, Papakostas GI, Nierenberg AA, Fava M. Brain white-matter hyperintensities and treatment outcome in major depressive disorder. Br J Psychiatry. 2006; 188:180-185.
• [10]Taylor W, Kamil K, Zheen Z, Steffens D, MacFall J. Cingulum bundle white matter lesions influence antidepressant response in late-life depression: Apilotstudy. J Affect Disord. 2014; 162:8-11.
• [11]Iosifescu DV, Clementi-Craven N, Fraguas R, Papakostas GI, Petersen T, Alpert JE, Nierenberg AA, Fava M. Cardiovascular risk factors may moderate pharmacological treatment effects in major depressive disorder. Psychosom Med. 2005; 67(5):703-706.
• [12]Sheline YI, Pieper CF, Barch DM, Welsh-Bohmer K, McKinstry RC, MacFall JR, D'Angelo G, Garcia KS, Gersing K, Wilkins C et al.. Support for the vascular depression hypothesis in late-life depression: results of a 2-site, prospective, antidepressant treatment trial. Arch Gen Psychiatry. 2010; 67(3):277-285.
• [13]Duman RS, Monteggia LM. A neurotrophic model for stress-related mood disorders. Biol Psychiatry. 2006; 59(12):1116-1127.
• [14]Breuillaud L, Rossetti C, Meylan EM, Merinat C, Halfon O, Magistretti PJ, Cardinaux JR. Deletion of CREB-regulated transcription coactivator 1 induces pathological aggression, depression-related behaviors, and neuroplasticity genes dysregulation in mice. Biol Psychiatry. 2012; 72(7):528-536.
• [15]Castren E, Rantamaki T. The role of BDNF and its receptors in depression and antidepressant drug action: Reactivation of developmental plasticity. Dev Neurobiol. 2010; 70(5):289-297.
• [16]Gudmundsson P, Skoog I, Waern M, Blennow K, Palsson S, Rosengren L, Gustafson D. The relationship between cerebrospinal fluid biomarkers and depression in elderly women. Am J Geriatr Psychiatry. 2007; 15(10):832-838.
• [17]Najjar S, Pearlman DM, Devinsky O, Najjar A, Zagzag D. Neurovascular unit dysfunction with blood–brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence. J Neuroinflammation. 2013; 10:142. BioMed Central Full Text
• [18]Zlokovic BV. Neurodegeneration and the neurovascular unit. Nat Med. 2010; 16(12):1370-1371.
• [19]Huang SJ, Zhang XH, Wang YY, Pan JH, Cui HM, Fang SP, Wu W, Zheng J, Li DJ, Bai G. Effects of Kaixin Jieyu Decoction on behavior, monoamine neurotransmitter levels, and serotonin receptor subtype expression in the brain of a rat depression model. Chin J Integr Med. 2014; 20(4):280-285.
• [20]Zhang XH, Huang SJ, Wang YY, Zhang Y, Pan JH, Zheng J, Li DJ, Lei XM. Effects of Kaixin Jieyu Decoction on behavior and glial fibrillary acidic protein expression in cerebral hippocampus of a rat vascular depression model. Chin J Integr Med. 2015; 21(3):223-228.
• [21]Hritcu L, Gorgan LD. Intranigral lipopolysaccharide induced anxiety and depression by altered BDNF mRNA expression in rat hippocampus. Prog Neuropsychopharmacol Biol Psychiatry. 2014; 51:126-132.
• [22]Kosel M, Brockmann H, Frick C, Zobel A, Schlaepfer TE. Chronic vagus nerve stimulation for treatment-resistant depression increases regional cerebral blood flow in the dorsolateral prefrontal cortex. Psychiatry Res. 2011; 191(3):153-159.
• [23]Liu X, Wang Z, Wang P, Yu B, Liu Y, Xue Y. Green tea polyphenols alleviate early BBB damage during experimental focal cerebral ischemia through regulating tight junctions and PKCalpha signaling. BMC Complement Altern Med. 2013; 13:187. BioMed Central Full Text
• [24]Yatomi Y, Tanaka R, Shimura H, Miyamoto N, Yamashiro K, Takanashi M, Urabe T, Hattori N. Chronic brain ischemia induces the expression of glial glutamate transporter EAAT2 in subcortical white matter. Neuroscience. 2013; 244:113-121.
• [25]Rinwa P, Kumar A, Garg S. Suppression of neuroinflammatory and apoptotic signaling cascade by curcumin alone and in combination with piperine in rat model of olfactory bulbectomy induced depression. PLoS One. 2013; 8(4): Article ID e61052
• [26]Isingrini E, Belzung C, D'Audiffret A, Camus V. Early and late-onset effect of chronic stress on vascular function in mice: a possible model of the impact of depression on vascular disease in aging. Am J Geriatr Psychiatry. 2011; 19(4):335-346.
• [27]Pan JH, Wang YY, Huang SJ, Mao YR, Chen Z, Zheng J, Li DJ, Cui HM. Establishment of Rat Model of Vascular Depression. Shou Du Yi Ke Da Xue Xue Bao. 2007; 28(6):760-762.
• [28]Choy M, Ganesan V, Thomas DL, Thornton JS, Proctor E, King MD, van der Weerd L, Gadian DG, Lythgoe MF. The chronic vascular and haemodynamic response after permanent bilateral common carotid occlusion in newborn and adult rats. J Cereb Blood Flow Metab. 2006; 26(8):1066-1075.
• [29]Otori T, Katsumata T, Muramatsu H, Kashiwagi F, Katayama Y, Terashi A. Long-term measurement of cerebral blood flow and metabolism in a rat chronic hypoperfusion model. Clin Exp Pharmacol Physiol. 2003; 30(4):266-272.
• [30]Youdim KA, Dobbie MS, Kuhnle G, Proteggente AR, Abbott NJ, Rice-Evans C. Interaction between flavonoids and the blood–brain barrier: in vitro studies. J Neurochem. 2003; 85(1):180-192.
• [31]Hwang SL, Shih PH, Yen GC. Neuroprotective effects of citrus flavonoids. J Agric Food Chem. 2012; 60(4):877-885.
• [32]Ye J, Lin H, Mu J, Cui X, Ying H, Lin M, Wu L, Weng J, Lin X. Effect of basic fibroblast growth factor on hippocampal cholinergic neurons in a rodent model of ischaemic encephalopathy. Basic Clin Pharmacol Toxicol. 2010; 107(6):931-939.
• [33]Shetty AK, Mishra V, Kodali M, Hattiangady B. Blood brain barrier dysfunction and delayed neurological deficits in mild traumatic brain injury induced by blast shock waves. Front Cell Neurosci. 2014; 8:232.
• [34]Takeda S, Sato N, Morishita R. Systemic inflammation, blood–brain barrier vulnerability and cognitive/non-cognitive symptoms in Alzheimer disease: relevance to pathogenesis and therapy. Front Aging Neurosci. 2014; 6:171.
• [35]Sato Y, Chin Y, Kato T, Tanaka Y, Tozuka Y, Mase M, Ageyama N, Ono F, Terao K, Yoshikawa Y et al.. White matter activated glial cells produce BDNF in a stroke model of monkeys. Neurosci Res. 2009; 65(1):71-78.
• [36]Yoshii A, Constantine-Paton M. Postsynaptic BDNF-TrkB signaling in synapse maturation, plasticity, and disease. Dev Neurobiol. 2010; 70(5):304-322.
• [37]Neeley EW, Berger R, Koenig JI, Leonard S. Prenatal stress differentially alters brain-derived neurotrophic factor expression and signaling across rat strains. Neuroscience. 2011; 187:24-35.
• [38]Collen D. The plasminogen (fibrinolytic) system. Thromb Haemost. 1999; 82(2):259-270.
• [39]Salles FJ, Strickland S. Localization and regulation of the tissue plasminogen activator-plasmin system in the hippocampus. J Neurosci. 2002; 22(6):2125-2134.
• [40]Eskandari F, Mistry S, Martinez PE, Torvik S, Kotila C, Sebring N, Drinkard BE, Levy C, Reynolds JC, Csako G et al.. Younger, premenopausal women with major depressive disorder have more abdominal fat and increased serum levels of prothrombotic factors: implications for greater cardiovascular risk. Metabolism. 2005; 54(7):918-924.
• [41]Tsai SJ, Hong CJ, Liou YJ, Yu YW, Chen TJ. Plasminogen activator inhibitor-1 gene is associated with major depression and antidepressant treatment response. Pharmacogenet Genomics. 2008; 18(10):869-875.
• [42]Tsai SJ. The possible role of tissue-type plasminogen activator and the plasminogen system in the pathogenesis of major depression. Med Hypotheses. 2006; 66(2):319-322.
• [43]Carrano A, Hoozemans JJ, van der Vies SM, Rozemuller AJ, van Horssen J, de Vries HE. Amyloid Beta induces oxidative stress-mediated blood–brain barrier changes in capillary amyloid angiopathy. Antioxid Redox Signal. 2011; 15(5):1167-1178.
• [44]Zlokovic BV. The blood–brain barrier in health and chronic neurodegenerative disorders. Neuron. 2008; 57(2):178-201.
• [45]Mishiro K, Ishiguro M, Suzuki Y, Tsuruma K, Shimazawa M, Hara H. A broad-spectrum matrix metalloproteinase inhibitor prevents hemorrhagic complications induced by tissue plasminogen activator in mice. Neuroscience. 2012; 205:39-48.
• [46]Shalev H, Serlin Y, Friedman A. Breaching the blood–brain barrier as a gate to psychiatric disorder. Cardiovasc Psychiatry Neurol. 2009; 2009:278531.
• [47]Lehner C, Gehwolf R, Tempfer H, Krizbai I, Hennig B, Bauer HC, Bauer H. Oxidative stress and blood–brain barrier dysfunction under particular consideration of matrix metalloproteinases. Antioxid Redox Signal. 2011; 15(5):1305-1323.
• [48]Nakaji K, Ihara M, Takahashi C, Itohara S, Noda M, Takahashi R, Tomimoto H. Matrix metalloproteinase-2 plays a critical role in the pathogenesis of white matter lesions after chronic cerebral hypoperfusion in rodents. Stroke. 2006; 37(11):2816-2823.
• [49]Tai SH, Chen HY, Lee EJ, Chen TY, Lin HW, Hung YC, Huang SY, Chen YH, Lee WT, Wu TS. Melatonin inhibits postischemic matrix metalloproteinase-9 (MMP-9) activation via dual modulation of plasminogen/plasmin system and endogenous MMP inhibitor in mice subjected to transient focal cerebral ischemia. J Pineal Res. 2010; 49(4):332-341.