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Dose-related effects of venlafaxine on pCREB and brain-derived neurotrophic factor (BDNF) in the hippocampus of the rat by chronic unpredictable stress

Published online by Cambridge University Press:  24 June 2014

Jing-Jing Li ,
Yong-Gui Yuan ,
Gang Hou  and
Xiang-Rong Zhang
Jing-Jing Li
Affiliation:
Department of Psychiatry, Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China
Yong-Gui Yuan*
Affiliation:
Department of Psychiatry, Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China Department of Neuropsychiatry, ZhongDa Hospital, Southeast University, Nanjing, China
Gang Hou
Affiliation:
Department of Psychiatry, Nanjing Brain Hospital, Nanjing Medical University, Nanjing, China
Xiang-Rong Zhang
Affiliation:
Department of Neuropsychiatry, ZhongDa Hospital, Southeast University, Nanjing, China
*
Yong-Gui Yuan, Department of Neuropsychiatry, ZhongDa Hospital, Southeast University, DingJiaQiao Road 87#, Nanjing 210009, China. Tel: +86 25 8370 0011/6209; Fax: +86 25 8370 9025; E-mail: [email protected]
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Extract

Background: The molecular pathogenesis of depression and psychopharmacology of antidepressants remain elusive. Recent hypotheses suggest that changes in neurogenesis and plasticity may underlie the aetiology of depression. The hippocampus is affected by depression and shows neuronal remodelling during adulthood.

Objective: The present study on the adult rat hippocampus, was to evaluate the dose-related effects of chronic venlafaxine on the expression of brain-derived neurotrophic factor (BDNF) and phosphorylated cyclic-AMP response element binding protein (pCREB).

Methods: Sprague-Dawley rats were exposed to a variety of chronic unpredictable stressors (CUSs) to establish a depression model. Rats were treated for either 14 or 28 days with venlafaxine (5 and 10 mg/kg, respectively). The hippocampal expression of pCREB and BDNF mRNA and protein was assessed by using immunohistochemistry, western blotting and reverse transcription polymerase chain reaction (RT-PCR).

Results: Rats subjected to CUS procedure consumed less sucrose solution compared with non-stressed rats. The CUS influenced exploratory activity resulting in a reduction of the motility counts. Chronic low dose (5 mg/kg, 14 and 28 days), but not high dose (10 mg/kg, 14 and 28 days) of venlafaxine treatment increased the expression of pCREB and BDNF mRNA and protein in the CUS rat hippocampus.

Conclusion: Neuronal plasticity-associated proteins such as pCREB and BDNF play an important role both in stress-related depression and in antidepressant effect.

Keywords

brain-derived neurotrophic factorchronic unpredictable stresscyclic-AMP response element binding proteinhippocampusneurogenesis
Type
Research Article
Information
Acta Neuropsychiatrica , Volume 23 , Issue 1 , February 2011 , pp. 20 - 30
Copyright
Copyright © Cambridge University Press 2011

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References

1.Brown, J, Cooper-Kuhn, CM, Kempermann, G et al. Enriched environment and physical activity stimulate hippocampal but not olfactory bulb neurogenesis. Eur J Neurosci 2003;17:2042–2046.Google Scholar
2.Willner, P.Validity, reliability and utility of the chronic mild stress model of depression: a 10-year review and evaluation. Psychopharmacology (Berl) 1997;134:319–329.Google Scholar
3.Willner, P.The validity of animal models of depression. Psychopharmacology (Berl) 1984;83:1–16.Google Scholar
4.Willner, P, Towell, A, Sampson, D, Sophokleous, S, Muscat, R.Reduction of sucrose preference by chronic unpredictable mild stress, and its restoration by a tricyclic antidepressant. Psychopharmacology (Berl) 1987;93:358–364.Google Scholar
5.Muscat, R, Papp, M, Willner, P.Reversal of stress-induced anhedonia by the atypical antidepressants, fluoxetine and maprotiline. Psychopharmacology (Berl) 1992;109:433–438.Google Scholar
6.Muscat, R, Papp, M, Willner, P.Antidepressant-like effects of dopamine agonists in an animal model of depression. Biol Psychiatry 1992;31:937–946.Google Scholar
7.Bondi, CO, Rodriguez, G, Gould, GG, Frazer, A, Morilak, DA.Chronic unpredictable stress induces a cognitive deficit and anxiety-like behavior in rats that is prevented by chronic antidepressant drug treatment. Neuropsychopharmacology 2008;33:320–331.Google Scholar
8.Duman, RS.Pathophysiology of depression: the concept of synaptic plasticity. Eur Psychiatry 2002;17 (Suppl. 3):306–310.Google Scholar
9.Duman, RS.Role of neurotrophic factors in the etiology and treatment of mood disorders. Neuromolecular Med 2004;5:11–25.Google Scholar
10.Duman, RS, Monteggia, LM.A neurotrophic model for stress-related mood disorders. Biol Psychiatry 2006;59:1116–1127.Google Scholar
11.Lindsay, RM, Wiegand, SJ, Altar, CA, DiStefano, PS.Neurotrophic factors: from molecule to man. Trends Neurosci 1994;17:182–190.Google Scholar
12.Smith, MA, Makino, S, Kvetnansky, R, Post, RM.Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci 1995;15:1768–1777.Google Scholar
13.Xu, H, Steven Richardson, J, Li, XM.Dose-related effects of chronic antidepressants on neuroprotective proteins BDNF, Bcl-2 and Cu/Zn-SOD in rat hippocampus. Neuropsychopharmacology 2003;28:53–62.Google Scholar
14.Shirayama, Y, Chen, AC, Nakagawa, S, Russell, DS, Duman, RS.Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. J Neurosci 2002;22:3251–3261.Google Scholar
15.Shaywitz, AJ, Greenberg, ME.CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu Rev Biochem 1999;68:821–861.Google Scholar
16.Nibuya, M, Morinobu, S, Duman, RS.Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci 1995;15:7539–7547.Google Scholar
17.Nibuya, M, Nestler, EJ, Duman, RS.Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus. J Neurosci 1996;16:2365–2372.Google Scholar
18.Nakagawa, S, Kim, JE, Lee, R et al. Localization of phosphorylated cAMP response element-binding protein in immature neurons of adult hippocampus. J Neurosci 2002;22:9868–9876.CrossRefGoogle ScholarPubMed
19.Rudolph, RL.Achieving remission from depression with venlafaxine and venlafaxine extended release: a literature review of comparative studies with selective serotonin reuptake inhibitors. Acta Psychiatr Scand Suppl 2002;415:24–30.CrossRefGoogle Scholar
20.Willner, P, Muscat, R, Papp, M.Chronic mild stress-induced anhedonia: a realistic animal model of depression. Neurosci Biobehav Rev 1992;16:525–534.Google Scholar
21.Kennett, GA, Dickinson, SL, Curzon, G.Enhancement of some 5-HT-dependent behavioural responses following repeated immobilization in rats. Brain Res 1985;330:253–263.Google Scholar
22.Katz, RJ, Roth, KA, Carroll, BJ.Acute and chronic stress effects on open field activity in the rat: implications for a model of depression. Neurosci Biobehav Rev 1981;5:247–251.Google Scholar
23.Gur, E, Dremencov, E, Lerer, B, Newman, ME.Venlafaxine: acute and chronic effects on 5-hydroxytryptamine levels in rat brain in vivo. Eur J Pharmacol 1999;372:17–24.Google Scholar
24.Willner, P.Chronic mild stress (CMS) revisited: consistency and behavioural-neurobiological concordance in the effects of CMS. Neuropsychobiology 2005;52:90–110.Google Scholar
25.Mao, QQ, Xian, YF, Ip, SP, Tsai, SH, Che, CT.Long-term treatment with peony glycosides reverses chronic unpredictable mild stress-induced depressive-like behavior via increasing expression of neurotrophins in rat brain. Behav Brain Res 2010;210:171–177.Google Scholar
26.Larsen, MH, Mikkelsen, JD, Hay-Schmidt, A, Sandi, C.Regulation of brain-derived neurotrophic factor (BDNF) in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment. J Psychiatr Res 2010;44:808–816.Google Scholar
27.Radley, JJ, Sisti, HM, Hao, J et al. Chronic behavioral stress induces apical dendritic reorganization in pyramidal neurons of the medial prefrontal cortex. Neuroscience 2004;125:1–6.Google Scholar
28.Sheline, YI, Gado, MH, Kraemer, HC.Untreated depression and hippocampal volume loss. Am J Psychiatry 2003;160:1516–1518.Google Scholar
29.Sheline, YI, Wang, PW, Gado, MH, Csernansky, JG, Vannier, MW.Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci U S A 1996;93:3908–3913.Google Scholar
30.Laifenfeld, D, Karry, R, Grauer, E, Klein, E, Ben-Shachar, D.Antidepressants and prolonged stress in rats modulate CAM-L1, laminin, and pCREB, implicated in neuronal plasticity. Neurobiol Dis 2005;20:432–441.CrossRefGoogle ScholarPubMed
31.Sairanen, M, O'Leary, OF, Knuuttila, JE, Castren, E.Chronic antidepressant treatment selectively increases expression of plasticity-related proteins in the hippocampus and medial prefrontal cortex of the rat. Neuroscience 2007;144:368–374.CrossRefGoogle ScholarPubMed
32.Davis, S, Vanhoutte, P, Pages, C, Caboche, J, Laroche, S.The MAPK/ERK cascade targets both Elk-1 and cAMP response element-binding protein to control long-term potentiation-dependent gene expression in the dentate gyrus in vivo. J Neurosci 2000;20:4563–4572.Google Scholar
33.Pham, TA, Impey, S, Storm, DR, Stryker, MP.CRE-mediated gene transcription in neocortical neuronal plasticity during the developmental critical period. Neuron 1999;22:63–72.Google Scholar
34.Taubenfeld, SM, Wiig, KA, Monti, B, Dolan, B, Pollonini, G, Alberini, CM.Fornix-dependent induction of hippocampal CCAAT enhancer-binding protein [beta] and [delta] co-localizes with phosphorylated cAMP response element-binding protein and accompanies long-term memory consolidation. J Neurosci 2001;21:84–91.Google Scholar
35.Viola, H, Furman, M, Izquierdo, LA et al. Phosphorylated cAMP response element-binding protein as a molecular marker of memory processing in rat hippocampus: effect of novelty. J Neurosci 2000;20:RC112.Google Scholar
36.Warner-Schmidt, JL, Duman, RS.Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment. Hippocampus 2006;16:239–249.Google Scholar
37.Xu, H, Chen, Z, He, J et al. Synergetic effects of quetiapine and venlafaxine in preventing the chronic restraint stress-induced decrease in cell proliferation and BDNF expression in rat hippocampus. Hippocampus 2006;16:551–559.Google Scholar
38.Thome, J, Sakai, N, Shin, K et al. cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment. J Neurosci 2000;20:4030– 4036.Google Scholar
39.Cremer, H, Chazal, G, Lledo, PM et al. PSA-NCAM: an important regulator of hippocampal plasticity. Int J Dev Neurosci 2000;18:213–220.Google Scholar
40.Li, J, Yuan, Y, Hou, G, Zhang, Z.Effects of chronic antidepressant venlafaxine on the expression of plasticity-related proteins mRNA in the hippocampus of the rat by chronic unpredictable stress. Chin J Psychiatry 2008;41:102–106Google Scholar
41.Sairanen, M, Lucas, G, Ernfors, P, Castren, M, Castren, E.Brain-derived neurotrophic factor and antidepressant drugs have different but coordinated effects on neuronal turnover, proliferation, and survival in the adult dentate gyrus. J Neurosci 2005;25:1089–1094.Google Scholar
42.Altar, CA, Whitehead, RE, Chen, R, Wortwein, G, Madsen, TM.Effects of electroconvulsive seizures and antidepressant drugs on brain-derived neurotrophic factor protein in rat brain. Biol Psychiatry 2003;54:703–709.Google Scholar
43.Dias, BG, Banerjee, SB, Duman, RS, Vaidya, VA.Differential regulation of brain derived neurotrophic factor transcripts by antidepressant treatments in the adult rat brain. Neuropharmacology 2003;45:553–563.Google Scholar
44.Coppell, AL, Pei, Q, Zetterstrom, TS.Bi-phasic change in BDNF gene expression following antidepressant drug treatment. Neuropharmacology 2003;44:903–910.Google Scholar
45.De Foubert, G, Carney, SL, Robinson, CS et al. Fluoxetine-induced change in rat brain expression of brain-derived neurotrophic factor varies depending on length of treatment. Neuroscience 2004;128:597–604.Google Scholar