Effects of Imipramine and Lithium on the Expression of Hippocampal Wnt 3a and Cyclin D1 in ACTH-Treated Rats

Yoshihisa Kitamura^1*, Hiromi Hayashi¹, Yuka Onoue¹, Keiko Kuwatsuka¹, Ayaka Miyake¹, Ikuko Miyazaki², Masato Asanuma², Toshiaki Sendo¹

¹Department of Clinical Pharmacy, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
²Department of Brain Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.

DOI: 10.4236/jbbs.2014.411048                

Abstract

We have shown previously that chronic administration of adrenocorticotropic hormone (ACTH) causes a significant decrease in hippocampal cell proliferation and neurogenesis. This effect in rats treated chronically with ACTH was not influenced by the chronic administration of imipramine, but was reversed by coadministration of imipramine and lithium. The present study was undertaken to further characterize the mechanism underlying the effect of imipramine and lithium on hippocampal cell proliferation and neurogenesis, by investigating the effects of treatment on the expression of brain-derived neurotrophic factor (BDNF), total cyclic adenosine monophosphate response element-binding protein (CREB), and phosphorylated CREB (pCREB) of the CREB signaling system, as well as Wnt 3a and cyclin D1 of the Wnt signaling pathway in the hippocampus of saline- and ACTH-treated rats. ACTH treatment significantly decreased the expression of cyclin D1. Treatment with imipramine and lithium increased the expression of cyclin D1 in ACTH-treated rats. However, the expression of BDNF, CREB, pCREB, and Wnt 3a did not change in either saline-treated or ACTH-treated rats. These findings suggest that the antidepressant effect of imipramine and lithium in ACTH-treatment-resistant rats may be attributed, at least in part, to an enhancement of cyclin D1 expression.

Keywords

Adrenocorticotropic Hormone, Imipramine, Lithium, Cyclin D1, Cell Proliferation

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Kitamura, Y., Araki, H. and Gomita, Y. (2002) Influence of ACTH on the Effects of Imipramine, Desipramine and Lithium on Duration of Immobility of Rats in the Forced Swim Test. Pharmacology, Biochemistry and Behavior, 71, 63-69. http://dx.doi.org/10.1016/S0091-3057(01)00625-6
[2]	Fink, M. (1990) How Does Convulsive Therapy Work? Neuropsychopharmacology, 3, 73-82.
[3]	Li, B., Suemaru, K., Cui, R., Kitamura, Y., Gomita, Y. and Araki, H. (2006) Repeated Electroconvulsive Stimuli Increase Brain-Derived Neurotrophic Factor in ACTH-Treated Rats. European Journal of Pharmacology, 529, 114-121. http://dx.doi.org/10.1016/j.ejphar.2005.11.009
[4]	Fuchs, E., Czeh, B. and Flugge, G. (2004) Examining Novel Concepts of the Pathophysiology of Depression in the Chronic Psychosocial Stress Paradigm in Tree Shrews. Behavioural Pharmacology, 15, 315-325. http://dx.doi.org/10.1097/00008877-200409000-00003
[5]	Malberg, J.E. and Duman, R.S. (2003) Cell Proliferation in Adult Hippocampus Is Decreased by Inescapable Stress: Reversal by Fluoxetine Treatment. Neuropsycho-pharmacology, 28, 1562-1571. http://dx.doi.org/10.1038/sj.npp.1300234
[6]	Kodama, M., Fujioka, T. and Duman, R.S. (2004) Chronic Olanzapine or Fluoxetine Administration Increases Cell Proliferation in Hippocampus and Prefrontal Cortex of Adult Rat. Biological Psychiatry, 56, 570-580. http://dx.doi.org/10.1016/j.biopsych.2004.07.008
[7]	Santarelli, L., Saxe, M., Gross, C., Surget, A., Battaglia, F., Dulawa, S., Weisstaub, N., Lee, J., Duman, R., Arancio, O., Belzung, C. and Hen, R. (2003) Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants. Science, 301, 805-809. http://dx.doi.org/10.1126/science.1083328
[8]	Doi, M., Miyazaki, I., Nagamachi, T., Shinomiya, K., Matsunaga, H., Sendo, T., Kawasaki, H., Asanuma, M., Gomita, Y. and Kitamura, Y. (2010) Effects of Imipramine and Lithium on the Suppression of Cell Proliferation in the Dentate Gyrus of the Hippocampus in Adrenocorticotropic Hormone-Treated Rats. Acta Medica Okayama, 64, 219-223.
[9]	Kitamura, Y., Doi, M., Kuwatsuka, K., Onoue, Y., Miyazaki, I., Shinomiya, K., Koyama, T., Sendo, T., Kawasaki, H., Asanuma, M. and Gomita, Y. (2011) Chronic Treatment with Imipramine and Lithium Increases Cell Proliferation in the Hippocampus in Adrenocorticotropic Hormone-Treated Rats. Biological and Pharmaceutical Bulletin, 34, 77-81. http://dx.doi.org/10.1248/bpb.34.77
[10]	Pencea, V., Bingaman, K.D., Wiegand, S.J. and Luskin, M.B. (2001) Infusion of Brain-Derived Neurotrophic Factor into the Lateral Ventricle of the Adult Rat Leads to New Neurons in the Parenchyma of the Striatum, Septum, Thalamus, and Hypothalamus. Journal of Neuroscience, 21, 6706-6717.
[11]	Schinder, A.F., Berninger, B. and Poo, M. (2000) Postsynaptic Target Specificity of Neurotrophin-Induced Presynaptic potentiation. Neuron, 25, 151-163. http://dx.doi.org/10.1016/S0896-6273(00)80879-X
[12]	Duman, R.S. and Monteggia, L.M. (2006) A Neurotrophic Model for Stress-Related Mood Disorders. Biological Psychiatry, 59, 1116-1127. http://dx.doi.org/10.1016/j.biopsych.2006.02.013
[13]	Post, R.M. (2007) Role of BDNF in Bipolar and Unipolar Disorder: Clinical and Theoretical Implications. Journal of Psychiatric Research, 41, 979-990. http://dx.doi.org/10.1016/j.jpsychires.2006.09.009
[14]	Kuipers, S.D., Trentani, A., van der Zee, E.A. and den Boer, J.A. (2013) Chronic Stress-Induced Changes in the Rat Brain: Role of Sex Differences and Effects of Long-Term Tianeptine Treatment. Neuropharmacology, 75, 426-436. http://dx.doi.org/10.1016/j.neuropharm.2013.08.018
[15]	Baldin, V., Lukas, J., Marcote, M.J., Pagano, M. and Draetta, G. (1993) Cyclin D1 Is a Nuclear Protein Required for Cell Cycle Progression in G1. Genes and Development, 7, 812-821. http://dx.doi.org/10.1101/gad.7.5.812
[16]	Matsushime, H., Quelle, D.E., Shurtleff, S.A., Shibuya, M., Sherr, C.J. and Kato, J.Y. (1994) D-Type Cyclin-Dependent Kinase Activity in Mammalian Cells. Molecular and Cellular Biology, 14, 2066-2076.
[17]	Meirmanov, S., Nakashima, M., Kondo, H., Matsufuji, R., Takamura, N., Ishigaki, K., Ito, M., Prouglo, Y., Yamashita, S. and Sekine, I. (2003) Correlation of Cytoplasmic Beta-Catenin and Cyclin D1 Overexpression during Thyroid Carcinogenesis around Semipalatinsk Nuclear Test Site. Thyroid, 13, 537-545. http://dx.doi.org/10.1089/105072503322238791
[18]	Nakashima, M., Meirmanov, S., Naruke, Y., Kondo, H., Saenko, V., Rogounovitch, T., Shimizu-Yoshida, Y., Takamura, N., Namba, H., Ito, M., Abrosimov, A., Lushnikov, E., Roumiantsev, P., Tsyb, A., Yamashita, S. and Sekine, I. (2004) Cyclin D1 Overexpression in Thyroid Tumours from a Radio-Contaminated Area and Its Correlation with Pin1 and Aberrant Beta-Catenin Expression. Journal of Pathology, 202, 446-455. http://dx.doi.org/10.1002/path.1534
[19]	Nelson, W.J. and Nusse, R. (2004) Convergence of Wnt, Beta-Catenin, and Cadherin Pathways. Science, 303, 1483-1487. http://dx.doi.org/10.1126/science.1094291
[20]	Lee, S.M., Tole, S., Grove, E. and McMahon, A.P. (2000) A Local Wnt-3a Signal Is Required for Development of the Mammalian Hippocampus. Development, 127, 457-467.
[21]	Chen, A.C., Shin, K.H., Duman, R.S. and Sanacora, G. (2001) ECS-Induced Mossy Fiber Sprouting and BDNF Expression Are Attenuated by Ketamine Pretreatment. Journal of ECT, 17, 27-32. http://dx.doi.org/10.1097/00124509-200103000-00006
[22]	Kuwatsuka, K., Hayashi, H., Onoue, Y., Miyazaki, I., Koyama, T., Asanuma, M., Kitamura, Y. and Sendo, T. (2013) The Mechanisms of Electroconvulsive Stimuli in BrdU-Positive Cells of the Dentate Gyrus in ACTH-Treated Rats. Journal of Pharmacological Sciences, 122, 34-41. http://dx.doi.org/10.1254/jphs.13015FP
[23]	Shtutman, M., Zhurinsky, J., Simcha, I., Albanese, C., D’Amico, M., Pestell, R. and Ben-Ze’ev, A. (1999) The Cyclin D1 Gene Is a Target of the Beta-Catenin/LEF-1 Pathway. Proceedings of the National Academy of Sciences of the United States of America, 96, 5522-5527. http://dx.doi.org/10.1073/pnas.96.10.5522
[24]	Tetsu, O. and McCormick, F. (1999) Beta-Catenin Regulates Expression of Cyclin D1 in Colon Carcinoma Cells. Nature, 398, 422-426. http://dx.doi.org/10.1038/18884
[25]	Kumar, D.U. and Devaraj, H. (2012) Expression of Wnt 3a, Beta-Catenin, Cyclin D1 and PCNA in Mouse Dentate Gyrus Subgranular Zone (SGZ): A Possible Role of Wnt Pathway in SGZ Neural Stem Cell Proliferation. Folia Biologica, 58, 115-120.
[26]	Gould, T.D., Einat, H., Bhat, R. and Manji, H.K. (2004) AR-A014418, a Selective GSK-3 Inhibitor, Produces Antidepressant-Like Effects in the Forced Swim Test. International Journal of Neuropsychopharmacology, 7, 387-390. http://dx.doi.org/10.1017/S1461145704004535
[27]	Jope, R.S. and Johnson, G.V. (2004) The Glamour and Gloom of Glycogen Synthase Kinase-3. Trends in Biochemical Sciences, 29, 95-102. http://dx.doi.org/10.1016/j.tibs.2003.12.004
[28]	Takahashi-Yanaga, F. and Sasaguri, T. (2007) The Wnt/Beta-Catenin Signaling Pathway as a Target in Drug Discovery. Journal of Pharmacological Sciences, 104, 293-302. http://dx.doi.org/10.1254/jphs.CR0070024