Anti-depressant-like effects of Jieyu chufan capsules in a mouse model of unpredictable chronic mild stress

Zhao,Hui; Liang,Bingyu; Yu,Linjie; Xu,Yun

doi:10.3892/etm.2017.4601

Anti-depressant-like effects of Jieyu chufan capsules in a mouse model of unpredictable chronic mild stress

Authors:
- Hui Zhao
- Bingyu Liang
- Linjie Yu
- Yun Xu
View Affiliations

Affiliations: Department of Neurology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu 210008, P.R. China
Published online on: June 14, 2017 https://doi.org/10.3892/etm.2017.4601
Pages: 1086-1094
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Jieyu chufan (JYCF) is a well-known Chinese traditional medicine used for depression; however, the molecular mechanism underlying its anti‑depressant action has remained elusive. In the present study, the anti‑depressant effects of JYCF and the potential mechanisms were investigated in a mouse model. Five groups of 12 C57BL/6 mice each were used in the study, including a normal control group (NC group), a model control group (MC group) and three groups, which received different doses of JYCF (1.25, 2.5 and 5 g/kg) orally for 21 days (JYCF groups). The MC group and the three JYCF groups were subjected to 3 weeks of unpredictable chronic mild stress (UCMS) to induce depression‑like behavior. All groups were subjected to a sucrose consumption test along with a forced swimming test to confirm depression‑like behavior, an open‑field test and an elevated plus maze test to confirm anxiety‑like behavior, and a Morris water maze test to evaluate spatial learning and memory. In addition, synaptic density in the hippocampus was evaluated and western blot and immunostaining were used to analyze hippocampal expression of postsynaptic density protein‑95 (PSD95), synaptophysin (Syn), cyclic adenosine monophosphate response element binding protein (CREB), brain‑derived neurotrophic factor (BDNF), Akt and glycogen synthase kinase (GSK)‑3β as well as their phosphorylated (p) versions. The results showed that JYCF (2.5 and 5 g/kg) alleviated depressive‑like behaviors and increased synaptic density in UCMS mice. Moreover, JYCF upregulated the expression of PSD95, Syn and BDNF and increased phosphorylated Akt, CREB and GSK‑3β in the hippocampus. These results suggested that JYCF exerts an anti‑depressant‑like activity in UCMS‑induced mice, which is likely to be mediated by reversing the stress‑induced disruption of BDNF and GSK-3β activity.

View Figures

View References

1	Aldao A, Mennin DS, Linardatos E and Fresco DM: Differential patterns of physical symptoms and subjective processes in generalized anxiety disorder and unipolar depression. J Anxiety Disord. 24:250–259. 2010. View Article : Google Scholar : PubMed/NCBI
2	Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, Ritz L, Norquist G, Howland RH, Lebowitz B, McGrath PJ, et al: Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: Implications for clinical practice. Am J Psychiatry. 163:28–40. 2006. View Article : Google Scholar : PubMed/NCBI
3	Rotheneichner P, Lange S, O'Sullivan A, Marschallinger J, Zaunmair P, Geretsegger C, Aigner L and Couillard-Despres S: Hippocampal neurogenesis and antidepressive therapy: Shocking relations. Neural Plast. 2014:7239152014. View Article : Google Scholar : PubMed/NCBI
4	Duman RS and Aghajanian GK: Synaptic dysfunction in depression: Potential therapeutic targets. Science. 338:68–72. 2012. View Article : Google Scholar : PubMed/NCBI
5	Wainwright SR and Galea LA: The neural plasticity theory of depression: Assessing the roles of adult neurogenesis and PSA-NCAM within the hippocampus. Neural Plast. 2013:8054972013. View Article : Google Scholar : PubMed/NCBI
6	Masi G and Brovedani P: The hippocampus, neurotrophic factors and depression: Possible implications for the pharmacotherapy of depression. CNS Drugs. 25:913–931. 2011. View Article : Google Scholar : PubMed/NCBI
7	Erickson KI, Miller DL and Roecklein KA: The aging hippocampus: Interactions between exercise, depression, and BDNF. Neuroscientist. 18:82–97. 2012. View Article : Google Scholar : PubMed/NCBI
8	Yoshii A and Constantine-Paton M: Postsynaptic BDNF-TrkB signaling in synapse maturation, plasticity, and disease. Dev Neurobiol. 70:304–322. 2010.PubMed/NCBI
9	Lipsky RH and Marini AM: Brain-derived neurotrophic factor in neuronal survival and behavior-related plasticity. Ann NY Acad Sci. 1122:130–143. 2007. View Article : Google Scholar : PubMed/NCBI
10	Schmidt HD and Duman RS: The role of neurotrophic factors in adult hippocampal neurogenesis, antidepressant treatments and animal models of depressive-like behavior. Behav Pharmacol. 18:391–418. 2007. View Article : Google Scholar : PubMed/NCBI
11	Castrén E, Võikar V and Rantamäki T: Role of neurotrophic factors in depression. Curr Opin Pharmacol. 7:18–21. 2007. View Article : Google Scholar : PubMed/NCBI
12	Aydemir C, Yalcin ES, Aksaray S, Kisa C, Yildirim SG, Uzbay T and Goka E: Brain-derived neurotrophic factor (BDNF) changes in the serum of depressed women. Prog Neuropsychopharmacol Biol Psychiatry. 30:1256–1260. 2006. View Article : Google Scholar : PubMed/NCBI
13	Hritcu L and Gorgan LD: Intranigral lipopolysaccharide induced anxiety and depression by altered BDNF mRNA expression in rat hippocampus. Prog Neuropsychopharmacol Biol Psychiatry. 51:126–132. 2014. View Article : Google Scholar : PubMed/NCBI
14	Musazzi L, Cattaneo A, Tardito D, Barbon A, Gennarelli M, Barlati S, Racagni G and Popoli M: Early raise of BDNF in hippocampus suggests induction of posttranscriptional mechanisms by antidepressants. BMC Neurosci. 10:482009. View Article : Google Scholar : PubMed/NCBI
15	Bradley CA, Peineau S, Taghibiglou C, Nicolas CS, Whitcomb DJ, Bortolotto ZA, Kaang BK, Cho K, Wang YT and Collingridge GL: A pivotal role of GSK-3 in synaptic plasticity. Front Mol Neurosci. 5:132012. View Article : Google Scholar : PubMed/NCBI
16	Liu W, Wang H, Wang Y, Li H and Ji L: Metabolic factors-triggered inflammatory response drives antidepressant effects of exercise in CUMS rats. Psychiatry Res. 228:257–264. 2015. View Article : Google Scholar : PubMed/NCBI
17	Klein PS and Melton DA: A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci USA. 93:pp. 8455–8459. 1996; View Article : Google Scholar : PubMed/NCBI
18	Kaidanovich-Beilin O, Milman A, Weizman A, Pick CG and Eldar-Finkelman H: Rapid antidepressive-like activity of specific glycogen synthase kinase-3 inhibitor and its effect on beta-catenin in mouse hippocampus. Biol Psychiatry. 55:781–784. 2004. View Article : Google Scholar : PubMed/NCBI
19	Shapira M, Licht A, Milman A, Pick CG, Shohami E and Eldar-Finkelman H: Role of glycogen synthase kinase-3beta in early depressive behavior induced by mild traumatic brain injury. Mol Cell Neurosci. 34:571–577. 2007. View Article : Google Scholar : PubMed/NCBI
20	Lao Y, Wang X, Xu N, Zhang H and Xu H: Application of proteomics to determine the mechanism of action of traditional Chinese medicine remedies. J Ethnopharmacol. 155:1–8. 2014. View Article : Google Scholar : PubMed/NCBI
21	Sun Y, Feng F and Yu X: Pharmacokinetics of geniposide in Zhi-Zi-Hou-Pu decoction and in different combinations of its constituent herbs. Phytother Res. 26:67–72. 2012. View Article : Google Scholar : PubMed/NCBI
22	Li JM, Kong LD, Wang YM, Cheng CH, Zhang WY and Tan WZ: Behavioral and biochemical studies on chronic mild stress models in rats treated with a Chinese traditional prescription Banxia-houpu decoction. Life Sci. 74:55–73. 2003. View Article : Google Scholar : PubMed/NCBI
23	Ma Z, Ji W, Qu R, Wang M, Yang W, Zhan Z, Fu Q and Ma S: Metabonomic study on the antidepressant-like effects of banxia houpu decoction and its action mechanism. Evid Based Complement Alternat Med. 2013:2137392013. View Article : Google Scholar : PubMed/NCBI
24	Willner P, Towell A, Sampson D, Sophokeous S and Muscat R: Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant. Psychopharmacology (Berl). 93:358–364. 1987. View Article : Google Scholar : PubMed/NCBI
25	Grippo AJ, Beltz TG, Weiss RM and Johnson AK: The effects of chronic fluoxetine treatment on chronic mild stress-induced cardiovascular changes and anhedonia. Biol Psychiatry. 59:309–316. 2006. View Article : Google Scholar : PubMed/NCBI
26	Benelli A, Filaferro M, Bertolini A and Genedani S: Influence of S-adenosyl-L-methionine on chronic mild stress-induced anhedonia in castrated rats. Br J Pharmacol. 127:645–654. 1999. View Article : Google Scholar : PubMed/NCBI
27	Forbes NF, Stewart CA, Matthews K and Reid IC: Chronic mild stress and sucrose consumption: Validity as a model of depression. Physiol Behav. 60:1481–1484. 1996. View Article : Google Scholar : PubMed/NCBI
28	Porsolt RD, Anton G, Blavet N and Jalfre M: Behavioural despair in rats: A new model sensitive to antidepressant treatments. Eur J Pharmacol. 47:379–391. 1978. View Article : Google Scholar : PubMed/NCBI
29	Zomkowski AD, Engel D, Gabilan NH and Rodrigues AL: Involvement of NMDA receptors and L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effects of escitalopram in the forced swimming test. Eur Neuropsychopharmacol. 20:793–801. 2010. View Article : Google Scholar : PubMed/NCBI
30	Iwamoto Y, Morinobu S, Takahashi T and Yamawaki S: Single prolonged stress increases contextual freezing and the expression of glycine transporter 1 and vesicle-associated membrane protein 2 mRNA in the hippocampus of rats. Prog Neuropsychopharmacol Biol Psychiatry. 31:642–651. 2007. View Article : Google Scholar : PubMed/NCBI
31	Yu L, Wang S, Chen X, Yang H, Li X, Xu Y and Zhu X: Orientin alleviates cognitive deficits and oxidative stress in Aβ1-42-induced mouse model of Alzheimer's disease. Life Sci. 121:104–109. 2015. View Article : Google Scholar : PubMed/NCBI
32	Ezzati A, Zimmerman ME, Katz MJ and Lipton RB: Hippocampal correlates of depression in healthy elderly adults. Hippocampus. 23:1137–1142. 2013. View Article : Google Scholar : PubMed/NCBI
33	Taylor WD, McQuoid DR, Payne ME, Zannas AS, MacFall JR and Steffens DC: Hippocampus atrophy and the longitudinal course of late-life depression. Am J Geriatr Psychiatry. 22:1504–1512. 2014. View Article : Google Scholar : PubMed/NCBI
34	André C, Dinel AL, Ferreira G, Layé S and Castanon N: Diet-induced obesity progressively alters cognition, anxiety-like behavior and lipopolysaccharide-induced depressive-like behavior: Focus on brain indoleamine 2,3-dioxygenase activation. Brain Behav Immun. 41:10–21. 2014. View Article : Google Scholar : PubMed/NCBI
35	Lupien SJ, Nair NP, Brière S, Maheu F, Tu MT, Lemay M, McEwen BS and Meaney MJ: Increased cortisol levels and impaired cognition in human aging: Implication for depression and dementia in later life. Rev Neurosci. 10:117–139. 1999. View Article : Google Scholar : PubMed/NCBI
36	Lucassen PJ, Stumpel MW, Wang Q and Aronica E: Decreased numbers of progenitor cells but no response to antidepressant drugs in the hippocampus of elderly depressed patients. Neuropharmacology. 58:940–949. 2010. View Article : Google Scholar : PubMed/NCBI
37	Ampuero E, Rubio FJ, Falcon R, Sandoval M, Diaz-Veliz G, Gonzalez RE, Earle N, Dagnino-Subiabre A, Aboitiz F, Orrego F and Wyneken U: Chronic floxetine treatment induces structural plasticity and selective changes in glutamate receptor subunits in the rat cerebral cortex. Neuroscience. 169:98–108. 2010. View Article : Google Scholar : PubMed/NCBI
38	Tanti A and Belzung C: Neurogenesis along the septo-temporal axis of the hippocampus: Are depression and the action of antidepressants region-specific? Neuroscience. 252:234–252. 2013. View Article : Google Scholar : PubMed/NCBI
39	Rayen I, Gemmel M, Pauley G, Steinbusch HW and Pawluski JL: Developmental exposure to SSRIs, in addition to maternal stress, has long-term sex-dependent effects on hippocampal plasticity. Psychopharmacology (Berl). 232:1231–1244. 2015. View Article : Google Scholar : PubMed/NCBI
40	Luoni A, Macchi F, Papp M, Molteni R and Riva MA: Lurasidone exerts antidepressant properties in the chronic mild stress model through the regulation of synaptic and neuroplastic mechanisms in the rat prefrontal cortex. Int J Neuropsychopharmacol. 18(pii): pyu0612014.PubMed/NCBI
41	Li W, Liu L, Liu YY, Luo J, Lin JY, Li X, Wang B and Min S: Effects of electroconvulsive stimulation on long-term potentiation and synaptophysin in the hippocampus of rats with depressive behavior. J ECT. 28:111–117. 2012. View Article : Google Scholar : PubMed/NCBI
42	Yulug B, Ozan E, Gönül AS and Kilic E: Brain-derived neurotrophic factor, stress and depression: A minireview. Brain Res Bull. 78:267–269. 2009. View Article : Google Scholar : PubMed/NCBI
43	Koch JM, Hinze-Selch D, Stingele K, Huchzermeier C, Goder R, Seeck-Hirschner M and Aldenhoff JB: Changes in CREB phosphorylation and BDNF plasma levels during psychotherapy of depression. Psychother Psychosom. 78:187–192. 2009. View Article : Google Scholar : PubMed/NCBI
44	Pláteník J, Fišar Z, Buchal R, Jirák R, Kitzlerová E, Zvěřová M and Raboch J: GSK-3β, CREB, and BDNF in peripheral blood of patients with Alzheimers disease and depression. Prog Neuropsychopharmacol Biol Psychiatry. 50:83–93. 2014. View Article : Google Scholar : PubMed/NCBI
45	Jope RS: Glycogen synthase kinase-3 in the etiology and treatment of mood disorders. Front Mol Neurosci. 4:162011. View Article : Google Scholar : PubMed/NCBI
46	Jope RS and Johnson GV: The glamour and gloom of glycogen synthase kinase-3. Trends Biochem Sci. 29:95–102. 2004. View Article : Google Scholar : PubMed/NCBI
47	Wada A: Lithium and neuropsychiatric therapeutics: Neuroplasticity via glycogen synthase kinase-3beta, beta-catenin, and neurotrophin cascades. J Pharmacol Sci. 110:14–28. 2009. View Article : Google Scholar : PubMed/NCBI
48	Zhang K, Song X, Xu Y, Li X, Liu P, Sun N, Zhao X, Liu Z, Xie Z and Peng J: Continuous GSK-3β overexpression in the hippocampal dentate gyrus induces prodepressant-like effects and increases sensitivity to chronic mild stress in mice. J Affect Disord. 146:45–52. 2013. View Article : Google Scholar : PubMed/NCBI
49	Silva R, Mesquita AR, Bessa J, Sousa JC, Sotiropoulos I, Leão P, Almeida OF and Sousa N: Lithium blocks stress-induced changes in depressive-like behavior and hippocampal cell fate: The role of glycogen-synthase-kinase-3beta. Neuroscience. 152:656–669. 2008. View Article : Google Scholar : PubMed/NCBI
50	Oh DH, Park YC and Kim SH: Increased glycogen synthase kinase-3β mRNA level in the hippocampus of patients with major depression: A study using the Stanley neuropathology consortium integrative database. Psychiatry Investig. 7:202–207. 2010. View Article : Google Scholar : PubMed/NCBI
51	Nayak G and Cooper GM: p53 is a major component of the transcriptional and apoptotic program regulated by PI3-kinase/Akt/GSK3 signaling. Cell Death Dis. 3:e4002012. View Article : Google Scholar : PubMed/NCBI
52	Kitagishi Y, Kobayashi M, Kikuta K and Matsuda S: Roles of PI3K/AKT/GSK-3/mTOR pathway in cell signaling of mental illnesses. Depress Res Treat. 2012:7525632012.PubMed/NCBI
53	Pláteník J, Fišar Z, Buchal R, Jirák R, Kitzlerová E, Zvěřová M and Raboch J: GSK3β, CREB, and BDNF in peripheral blood of patients with Alzheimer's disease and depression. Prog Neuropsychopharmacol Biol Psychiatry. 50:83–93. 2014. View Article : Google Scholar : PubMed/NCBI