Antidepressant-Like Effects of Central BDNF Administration in Mice of Antidepressant Sensitive Catalepsy (ASC) Strain

10.4077/CJP.2012.BAA041

Maria A. Tikhonova；Alexander V. Kulikov；Daria V. Bazovkina；Maryana V. Morozova；Vladimir S. Naumenko；and Nina K. Popova

BDNF ； animal model ； antidepressant-like activity ； behavior ； Arc mRNA ； mice

The Chinese Journal of Physiology

55卷4期（2012 / 08 / 01）

284 - 293

英文

Although numerous data evidence the implication of brain-derived neurotrophic factor (BDNF) in the pathophysiology of depression, the potential for BDNF to correct genetically defined depressive-like states is poorly studied. This study was aimed to reveal antidepressant-like effects of BDNF (300 ng, 2×, i.c.v.) on behavior and mRNA expression of genes associated with depression-like state in the brain in mice of antidepressant sensitive catalepsy (ASC) strain characterized by high hereditary predisposition to catalepsy and depressive-like features. Behavioral tests were held on the 7th-16th days after the first (4th-13th after the second) BDNF injection. Results showed that BDNF normalized impaired sexual motivation in the ASC males, and this BDNF effect differed, with advantageous effects, from that of widely used antidepressants. The anticataleptic effect of two BDNF injections was enhanced compared with a single administration. A tendency to decrease the immobility duration in tail-suspension test was observed in BDNF-treated ASC mice. The effects on catalepsy and sexual motivation were specific since BDNF did not alter locomotor and exploratory activity or social interest in the ASC mice. Along with behavioral antidepressant-like effects on the ASC mice, BDNF increased hippocampal mRNA levels of Bdnf and Creb1 (cAMP response element-binding protein gene). BDNF also augmented mRNA levels of Arc gene encoding Arc (Activity-regulated cytoskeleton-associated) protein involved in BDNF-induced processes of neuronal and synaptic plasticity in hippocampus and prefrontal cortex. The data suggest that: BDNF is effective in the treatment of some genetically defined behavioral disturbances; BDNF influences sexually-motivated behavior; Arc mRNA levels may serve as a molecular marker of BDNF physiological activity associated with its long-lasting behavioral effects; ASC mouse strain can be used as a suitable model to study mechanisms of BDNF effects on hereditary-dependent behavioral disorders.

1. Aid, T.,Kazantseva, A.,Piirsoo, M.,Palm, K.,Timmusk, T.(2007).Mouse and rat BDNF gene structure and expression revisited.J. Neurosci. Res.,85,525-535.
2. Alme, M.N.,Wibrand, K.,Dagestad, G.,Bramham, C.R.(2007).Chronic fluoxetine treatment induces brain region-specific upregulation of genes associated with BDNF-induced long-term potentiation.Neural Plast.
3. Alperina, E.L.,Kulikov, A.V.,Popova, N.K.,Idova, G.V.(2007).Immnune response in mice of a new strain ASC (antidepressants sensitive catalepsy).Bull. Exp. Biol. Med.,144,221-223.
4. Amstislavskaia, T.G.,Gladkikh, D.V.,Belousova, I.I.,Maslova, L.N.,Popova, N.K.(2010).The influence of sexual experience on sexual motivation and copulatory behavior in male rats.Ross. Fiziol. Zh. Im. I. M. Sechenova.,96,154-162.
5. Amstislavskaya, T.G.,Popova, N.K.(2004).Female-induced sexual arousal in male mice and rats: behavioral and testosterone response.Horm. Behav.,46,544-550.
6. Balu, D.T.,Hoshaw, B.A.,Malberg, J.E.,Rosenzweig-Lipson, S.,Schechter, L.E.,Lucki, I.(2008).Differential regulation of central BDNF protein levels by antidepressant and non-antidepressant drug treatments.Brain Res.,1211,37-43.
7. Barde, Y.A.(1990).The nerve growth factor family.Prog. Growth Factor Res.,2(4),237-248.
8. Bazovkina, D.V.,Kulikova, A.V.,Kondaurova, E.M.,Popova, N.K.(2005).Selection for the predisposition to catalepsy enhances depressive-like traits in mice.Genetika,41,1222-1228.
9. Bramham, C.R.,Worley, P.F.,Moore, M.J.,Guzowski, J.F.(2008).The immediate early gene arc/arg3.1: regulation, mechanisms, and function.J. Neurosci.,28,11760-11767.
10. Brunoni, A.R.,Lopes, M.,Fregni, F.(2008).A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression.Int. J. Neuropsychopharmacol.,11(8),1169-1180.
11. Castren, E.(2004).Neurotrophic effects of antidepressant drugs.Curr. Opin. Pharmacol.,4(1),58-64.
12. Castren, E.,Rantamaki, T.(2010).The role of BDNF and its receptors in depression and antidepressant drug action: Reactivation of developmental plasticity.Dev. Neurobiol.,70,289-297.
13. Castro, E.,Tordera, R.M.,Hughes, Z.A.,Pei, Q.,Sharp, T.(2003).Use of Arc expression as a molecular marker of increased postsynaptic 5-HT function after SSRI/5-HT1A receptor antagonist co-administration.J. Neurochem.,85,1480-1487.
14. Clayton, A.H.,Montejo, A.L.(2006).Major depressive disorder, antidepressants, and sexual dysfunction.J. Clin. Psychiatry,67(Suppl 6),33-37.
15. Cryan, J.F.,Markou, A.,Lucki, I.(2002).Assessing antidepressant activity in rodents: recent developments and future needs.Trends Pharmacol. Sci.,23,238-245.
16. De Foubert, G.,Carney, S.L.,Robinson, C.S.,Destexhe, E.J.,Tomlinson, R.,Hicks, C.A.,Murray, T.K.,Gaillard, J.P.,Deville, C.,Xhenseval, V.,Thomas, C.E.,O''Neill, M.J.,Zetterstrom, T.S.(2004).Fluoxetine-induced change in rat brain expression of brain-derived neurotrophic factor varies depending on length of treatment.Neuroscience,128,597-604.
17. Dixon, A.K.(1998).Ethological strategies for defence in animals and humans: their role in some psychiatric disorders.Brit. J. Med. Psychol.,71,417-445.
18. Dubrovina, N.I.,Zinov''ev, D.R.,Zinov''eva, D.V.,Kulikov, A.V.(2009).Learning and extinction of a passive avoidance response in mice with high levels of predisposition to catalepsy.Neurosci. Behav. Physiol.,39,475-480.
19. El-Sayed, M.,Hofman-Bang, J.,Mikkelsen, J.D.(2011).Effect of brain-derived neurotrophic factor on activity-regulated cytoskeleton-associated protein gene expression in primary frontal cortical neurons. Comparison with NMDA and AMPA.Eur. J. Pharmacol.,660,351-357.
20. Finkbeiner, S.,Tavazoie, S.F.,Maloratsky, A.,Jacobs, K.M.,Harris, K.M.,Greenberg, M.E.(1997).CREB: a major mediator of neuronal neurotrophin responses.Neuron,19,1031-1047.
21. Gourley, S.L.,Kiraly, D.D.,Howell, J.L.,Olausson, P.,Taylor, J.R.(2008).Acute hippocampal brain-derived neurotrophic factor restores motivational and forced swim performance after corticosterone.Biol. Psychiatry,64,884-890.
22. Greenwood, B.N.,Strong, P.V.,Foley, T.E.,Thompson, R.S.,Fleshner, M.(2007).Learned helplessness is independent of levels of brain-derived neurotrophic factor in the hippocampus.Neuroscience,144,1193-1208.
23. Gregorian, R.S.,Golden, K.A.,Bahce, A.,Goodman, C.,Kwong, W.J.,Khan, Z.M.(2002).Antidepressant-induced sexual dysfunction.Ann. Pharmacother.,36,1577-1589.
24. Hellweg, R.,Ziegenhorn, A.,Heuser, I.,Deuschle, M.(2008).Serum concentrations of nerve growth factor and brain-derived neurotrophic factor in depressed patients before and after antidepressant treatment.Pharmacopsychiatry,41,66-71.
25. Henry, C.J.,Huang, Y.,Wynne, A.,Hanke, M.,Himler, J.,Bailey, M.T.,Sheridan, J.F.,Godbout, J.P.(2008).Minocycline attenuates lipopolysaccharide (LPS)-induced neuroinflammation, sickness behavior, and anhedonia.J. Neuroinflamm.,5,15.
26. Hoshaw, B.A.,Malberg, J.E.,Lucki, I.(2005).Central administration of IGF-I and BDNF leads to long-lasting antidepressant-like effects.Brain Res.,1037,204-208.
27. Itoh, T.,Tokumura, M.,Abe, K.(2004).Effects of rolipram, a phosphodiesterase 4 inhibitor, in combination with imipramine on depressive behavior, CRE-binding activity and BDNF level in learned helplessness rats.Eur. J. Pharmacol.,498,135-142.
28. Ji, Y.,Lu, Y.,Yang, F.,Shen, W.,Tang, T.T.,Feng, L.,Duan, S.,Lu, B.(2010).Acute and gradual increases in BDNF concentration elicit distinct signaling and functions in neurons.Nat. Neurosci.,13,302-309.
29. Klemm, W.R.(1989).Drug effects on active immobility responses: what they tell us about neurotransmitter systems and motor functions.Prog. Neurobiol.,32,403-422.
30. Kondaurova, E.M.,Bazovkina, D.V.,Kulikov, A.V.,Popova, N.K.(2006).Selective breeding for catalepsy changes the distribution of microsatellite D13Mit76 alleles linked to the 5-HT serotonin receptor gene in mice.Genes Brain Behav.,5(8),596-601.
31. Kulikov, A.V.(ed.)(2006).Animal Models in Biological Psychiatry.New York:Nova Science Publishers.
32. Kulikov, A.V.,Bazovkina, D.V.,Kondaurova, E.M.,Popova, N.K.(2008).Genetic structure of hereditary catalepsy in mice.Genes Brain Behav.,7(4),506-512.
33. Kulikov, A.V.,Kozlachkova, E.Y.,Maslova, G.B.,Popova, N.K.(1993).Inheritance of predisposition to catalepsy in mice.Behav. Genet.,23,379-384.
34. Kulikov, A.V.,Naumenko, V.S.,Voronova, I.P.,Tikhonova, M.A.,Popova, N.K.(2005).Quantitative RT-PCR assay of 5-HT1A and 5-HT2A serotonin receptor mRNAs using genomic DNA as an external standard.J. Neurosci. Methods,141,97-101.
35. Kulikov, A.V.,Tikhonova, M.A.,Kulikov, V.A.(2008).Automated measurement of spatial preference in the open field test with transmitted lighting.J. Neurosci. Methods,170,345-351.
36. Larsen, M.H.,Rosenbrock, H.,Sams-Dodd, F.,Mikkelsen, J.D.(2007).Expression of brain derived neurotrophic factor, activity-regulated cytoskeleton protein mRNA, and enhancement of adult hippocampal neurogenesis in rats after sub-chronic and chronic treatment with the triple monoamine re-uptake inhibitor tesofensine.Eur. J. Pharmacol.,555,115-121.
37. Lee, H.Y.,Kim, Y.K.(2008).Plasma brain-derived neurotrophic factor as a peripheral marker for the action mechanism of antidepressants.Neuropsychobiology,57,194-199.
38. Messaoudi, E.,Kanhema, T.,Soule, J.,Tiron, A.,Dagyte, G.,da Silva, B.,Bramham, C.R.(2007).Sustained Arc/Arg3.1 synthesis controls long-term potentiation consolidation through regulation of local actin polymerization in the dentate gyrus in vivo.J. Neurosci.,27,10445-10455.
39. Naumenko, V.S.,Bazovkina, D.V.,Kondaurova, E.M.,Zubkov, E.A.,Kulikov, A.V.(2010).The role of 5-HT2A receptor and 5-HT2A/5-HT1A receptor interaction in the suppression of catalepsy.Genes Brain Behav.,9(5),519-524.
40. Naumenko, V.S.,Kulikov, A.V.(2006).Quantitative assay of 5-HT1A serotonin receptor gene expression in the brain.Mol. Biol. (Mosk),40,37-44.
41. Naumenko, V.S.,Osipova, D.V.,Kostina, E.V.,Kulikov, A.V.(2008).Utilization of a two-standard system in real-time PCR for quantification of gene expression in the brain.J. Neurosci. Methods,170,197-203.
42. Nibuya, M.,Morinobu, S.,Duman, R.S.(1995).Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments.J. Neurosci.,15,7539-7547.
43. Pei, Q.,Zetterstrom, T.S.,Sprakes, M.,Tordera, R.,Sharp, T.(2003).Antidepressant drug treatment induces Arc gene expression in the rat brain.Neuroscience,121,975-982.
44. Pittenger, C.,Duman, R.S.(2008).Stress, depression, and neuroplasticity: a convergence of mechanisms.Neuropsychopharmacology,33,88-109.
45. Rogoz, Z.,Legutko, B.(2005).Combined treatment with imipramine and metyrapone induces hippocampal and cortical brain-derived neurotrophic factor gene expression in rats.Pharmacol. Rep.,57,840-844.
46. Sanberg, P.R.,Bunsey, M.D.,Giordano, M.,Norman, A.B.(1988).The catalepsy test: its ups and downs.Behav. Neurosci.,102,748-759.
47. Schmidt, H.D.,Banasr, M.,Duman, R.S.(2008).Future antidepressant targets: neurotrophic factors and related signaling cascades.Drug Discov. Today Ther. Strateg.,5(3),151-156.
48. Sen, S.,Duman, R.,Sanacora, G.(2008).Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications.Biol. Psychiatry,64,527-532.
49. Shirayama, Y.,Chen, A.C.,Nakagawa, S.,Russell, D.S.,Duman, R.S.(2002).Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression.J. Neurosci.,22,3251-3261.
50. Singerman, B.,Raheja, R.(1994).Malignant catatonia-a continuing reality.Ann. Clin. Psychiatry,6(4),259-266.
51. Sinovyev, D.R.,Dubrovina, N.I.,Kulikov, A.V.(2009).Development of amnesia in different mouse strains.Bull. Exp. Biol. Med.,147,557-559.
52. Sirianni, R.W.,Olausson, P.,Chiu, A.S.,Taylor, J.R.,Saltzman, W.M.(2010).The behavioral and biochemical effects of BDNF containing polymers implanted in the hippocampus of rats.Brain Res.,1321,40-50.
53. Soule, J.,Messaoudi, E.,Bramham, C.R.(2006).Brain-derived neurotrophic factor and control of synaptic consolidation in the adult brain.Biochem. Soc. Trans.,34,600-604.
54. Taylor, M.A.,Fink, M.(2003).Catatonia in psychiatric classification: a home of its own.Am. J. Psychiatry,160,1233-1241.
55. Thome, J.,Sakai, N.,Shin, K.,Steffen, C.,Zhang, Y.J.,Impey, S.,Storm, D.,Duman, R.S.(2000).cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment.J. Neurosci.,20,4030-4036.
56. Tikhonova, M.A.,Alperina, E.L.,Tolstikova, T.G.,Bazovkina, D.V.,Di, V.Y.,Idova, G.V.,Kulikov, A.V.,Popova, N.K.(2010).Effects of chronic fluoxetine treatment on catalepsy and the immune response in mice with a genetic predisposition to freezing reactions: the roles of types 1A and 2A serotonin receptors and the tph2 and SERT genes.Neurosci. Behav. Physiol.,40,521-527.
57. Tikhonova, M.A.,Kulikov, A.V.,Naumenko, V.S.,Morozova, M.V.,Bazovkina, D.V.,Popova, N.K.(2009).Intracerebral administration of brain-derived neurotrophic factor (BDNF) reduces severity of cataleptic freezing in mice with genetic predisposition to catalepsy.Bull. Exp. Biol. Med.,148,889-891.
58. Tikhonova, M.A.,Lebedeva, V.V.,Kulikov, A.V.,Bazovkina, D.V.,Popova, N.K.(2006).Effect of imipramine on the behavior and cerebral 5-HT1A serotonin receptors in mice genetically predisposed to catalepsy.Bull. Exp. Biol. Med.,141,48-50.
59. Tikhonova, M.A.,Otroshchenko, E.A.,Kulikov, A.V.(2010).Effects of chronic fluoxetine treatment on manifestation of sexual motivation and social behavior in mice of ASC line.Ross. Fiziol. Zh. Im. I. M. Sechenova,96,163-172.
60. Torres, S.L.(ed.),Marin, M.S.(ed.)(2008).Genetic Predisposition to Disease.NewYork:Nova Science Publishers.
61. Vishnivetskaya, G.B.,Skrinskaya, J.A.,Seif, I.,Popova, N.K.(2007).Effect of MAO A deficiency on different kinds of aggression and social investigation in mice.Aggressive Behav.,33,1-6.
62. Wibrand, K.,Messaoudi, E.,Havik, B.,Steenslid, V.,Lovlie, R.,Steen, V.M.,Bramham, C.R.(2006).Identification of genes co-upregulated with Arc during BDNF-induced long-term potentiation in adult rat dentate gyrus in vivo.Eur. J. Neurosci.,23,1501-1511.
63. Ying, S.W.,Futter, M.,Rosenblum, K.,Webber, M.J.,Hunt, S.P.,Bliss, T.V.,Bramham, C.R.(2002).Brain-derived neurotrophic factor induces long-term potentiation in intact adult hippocampus: requirement for ERK activation coupled to CREB and upregulation of Arc synthesis.J. Neurosci.,22,1532-1540.