Skip to main content
SpringerLink
Log in
Book cover

Taurine 8 pp 29–43Cite as

Antidepressant-Like Effect of Chronic Taurine Administration and Its Hippocampal Signal Transduction in Rats

  • Conference paper
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 775))

Abstract

Taurine is one of the most abundant amino acids in the central nervous system, and it has various important functions as a neuromodulator and antioxidant. Taurine is expected to be involved in the mental disorders such as depression; however, knowledge of its function in relation to depression is limited. In this research, we tried to elucidate the effects of taurine supplementation on antidepressant-like behaviors in rats and depression-related signal transduction in the hippocampus. In behavioral tests, rats fed a high taurine (HT: 45 mmol/kg taurine) diet for 4 weeks (HT4w) showed decreased immobility in the forced swim test (FS) compared to controls. On the other hand, rats fed a low taurine (LT: 22.5 mmol/kg taurine) diet for 4 weeks or an HT diet for 2 weeks (HT2w) did not show a significant difference in FS compared to controls. In western blot analyses, the expression of glutamic acid decarboxylase (GAD) 65 and GAD67 in the hippocampus was not affected by taurine supplementation. However, the phosphorylation levels of extracellular signal-regulated kinase1/2 (ERK1/2), protein kinase B (Akt), glycogen synthase kinase3 beta (GSK3β), and cAMP response element-binding protein (CREB) were increased in the hippocampus of HT4w and HT2w rats. Phosphorylated calcium/calmodulin-dependent protein kinase II (CaMKII) was increased in the hippocampus of HT4w rats only. Moreover, no significant changes in these molecules were observed in the hippocampus of rats fed an HT diet for 1 day. In conclusion, our discoveries suggest that taurine supplementation has an antidepressant-like effect and an ability to change depression-related signaling cascades in the hippocampus.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Abbreviations

HT:

High taurine

LT:

Low taurine

FS:

Forced swim test

GAD:

Glutamic acid decarboxylase

ERK1/2:

Extracellular signal-regulated kinase1/2

Akt:

Protein kinase B

GSK3β:

Glycogen synthase kinase3 beta

CREB:

cAMP response element-binding protein

CaMKII:

Calcium/calmodulin-dependent protein kinase II

References

  • Albrecht J, Schousboe A (2005) Taurine interaction with neurotransmitter receptors in the CNS: an update. Neurochem Res 30:1615–1621

    Article  PubMed  CAS  Google Scholar 

  • Altamura C, Maes M, Dai J, Meltzer HY (1995) Plasma concentrations of excitatory amino acids, serine, glycine, taurine and histidine in major depression. Eur Neuropsychopharmacol 5(Suppl):71–75

    Article  PubMed  CAS  Google Scholar 

  • Barbiero VS, Giambelli R, Musazzi L, Tiraboschi E, Tardito D, Perez J, Drago F, Racagni G, Popoli M (2007) Chronic antidepressants induce redistribution and differential activation of alphaCaM kinase II between presynaptic compartments. Neuropsychopharmacology 32:2511–2519

    Article  PubMed  CAS  Google Scholar 

  • Berton O, Nestler EJ (2006) New approaches to antidepressant drug discovery: beyond monoamines. Nat Rev Neurosci 7:137–151

    Article  PubMed  CAS  Google Scholar 

  • Bonanno G, Giambelli R, Raiteri L, Tiraboschi E, Zappettini S, Musazzi L, Raiteri M, Racagni G, Popoli M (2005) Chronic antidepressants reduce depolarization-evoked glutamate release and protein interactions favoring formation of SNARE complex in hippocampus. J Neurosci 25: 3270–3279

    Article  PubMed  CAS  Google Scholar 

  • Chen SW, Kong WX, Zhang YJ, Li YL, Mi XJ, Mu XS (2004) Possible anxiolytic effects of taurine in the mouse elevated plus-maze. Life Sci 75:1503–1511

    Article  PubMed  CAS  Google Scholar 

  • del Olmo N, Bustamante J, del Río RM, Solís JM (2000a) Taurine activates GABA(A) but not GABA(B) receptors in rat hippocampal CA1 area. Brain Res 864:298–307

    Article  PubMed  Google Scholar 

  • del Olmo N, Galarreta M, Bustamante J, Martín del Rio R, Solís JM (2000b) Taurine-induced synaptic potentiation: role of calcium and interaction with LTP. Neuropharmacology 39: 40–54

    Article  PubMed  Google Scholar 

  • del Olmo N, Handler A, Alvarez L, Bustamante J, Martín del Río R, Solís JM (2003) Taurine-induced synaptic potentiation and the late phase of long-term potentiation are related mechanistically. Neuropharmocology 44:26–39

    Article  Google Scholar 

  • Do KQ, Lauer CJ, Schreiber W, Zollinger M, Gutteck-Amsler U, Cuénod M, Holsboer F (1995) Gamma-Glutamylglutamine and taurine concentrations are decreased in the cerebrospinal fluid of drug-naive patients with schizophrenic disorders. J Neurochem 65:2652–2662

    Article  PubMed  CAS  Google Scholar 

  • Du K, Montminy M (1998) CREB is a regulatory target for the protein kinase Akt/PKB. J Biol Chem 273:32377–32379

    Article  PubMed  CAS  Google Scholar 

  • Fatemi SH, Reutiman TJ, Folsom TD, Huang H, Oishi K, Mori S, Smee DF, Pearce DA, Winter C, Sohr R, Maternal JG (2008) Maternal infection leads to abnormal gene regulation and brain atrophy in mouse offspring: implications for genesis of neurodevelopmental disorders. Schizophr Res 99:56–70

    Article  PubMed  Google Scholar 

  • Fukuo Y, Kishi T, Kushima I, Yoshimura R, Okochi T, Kitajima T, Matsunaga S, Kawashima K, Umene-Nakano W, Naitoh H, Inada T, Nakamura J, Ozaki N, Iwata N (2011) Possible association between ubiquitin-specific peptidase 46 gene and major depressive disorders in the Japanese population. J Affect Disord 133:150–157

    Article  PubMed  CAS  Google Scholar 

  • Galarreta M, Bustamante J, Martin del Río R, Solís JM (1996) Taurine induces a long-lasting increase of synaptic efficacy and axon excitability in the hippocampus. J Neurosci 16:92–102

    PubMed  CAS  Google Scholar 

  • Grimes CA, Jope RS (2001) CREB DNA binding activity is inhibited by glycogen synthase kinase-3 beta and facilitated by lithium. J Neurochem 78:1219–1232

    Article  PubMed  CAS  Google Scholar 

  • Han F, Nakano T, Yamamoto Y, Shioda N, Lu YM, Fukunaga K (2009) Improvement of depressive behaviors by nefiracetam is associated with activation of CaM kinases in olfactory bulbectomized mice. Brain Res 1265:205–214

    Article  PubMed  CAS  Google Scholar 

  • Hernández-Benítez R, Pasantes-Morales H, Saldaña IT, Ramos-Mandujano G (2010) Taurine stimulates proliferation of mice embryonic cultured neural progenitor cells. J Neurosci Res 88:1673–1681

    PubMed  Google Scholar 

  • Hussy N, Deleuze C, Desarménien MG, Moos FC (2000) Osmotic regulation of neuronal activity: a new role for taurine and glial cells in a hypothalamic neuroendocrine structure. Prog Neurobiol 62:113–134

    Article  PubMed  CAS  Google Scholar 

  • Iio W, Matsukawa N, Tsukahara T, Kohari D, Toyoda A (2011) Effects of chronic social defeat stress on MAP kinase cascade. Neurosci Lett 504:281–284

    Article  PubMed  CAS  Google Scholar 

  • Inan SY, Yalcin I, Aksu F (2004) Dual effects of nitric oxide in the mouse forced swimming test: possible contribution of nitric oxide-mediated serotonin release and potassium channel modulation. Pharmacol Biochem Behav 77:457–464

    Article  PubMed  CAS  Google Scholar 

  • Jeon SH, Lee MY, Kim SJ, Joe SG, Kim GB, Kim IS, Kim NS, Hong CU, Kim SZ, Kim JS, Kang HS (2007) Taurine increases cell proliferation and generates an increase in [Mg2+]i accompanied by ERK 1/2 activation in human osteoblast cells. FEBS Lett 581:5929–5934

    Article  PubMed  CAS  Google Scholar 

  • Junyent F, Romero R, de Lemos L, Utrera J, Camins A, Pallàs M, Auladell C (2010) Taurine treatment inhibits CaMKII activity and modulates the presence of calbindin D28k, calretinin, and parvalbumin in the brain. J Neurosci Res 88:136–142

    Article  PubMed  CAS  Google Scholar 

  • Karege F, Perroud N, Burkhardt S, Schwald M, Ballmann E, La Harpe R, Malafosse A (2007) Alteration in kinase activity but not in protein levels of protein kinase B and glycogen synthase kinase-3beta in ventral prefrontal cortex of depressed suicide victims. Biol Psychiatry 61:240–245

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi K, Ikeda Y, Sakai A, Yamasaki N, Haneda E, Miyakawa T, Suzuki H (2010) Reversal of hippocampal neuronal maturation by serotonergic antidepressants. Proc Natl Acad Sci USA 107:8434–8439

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi K, Ikeda Y, Suzuki H (2011) Behavioral destabilization induced by the selective serotonin reuptake inhibitor fluoxetine. Mol Brain 4:12

    Article  PubMed  CAS  Google Scholar 

  • Kong WX, Chen SW, Li YL, Zhang YJ, Wang R, Min L, Mi X (2006) Effects of taurine on rat behaviors in three anxiety models. Pharmacol Biochem Behav 83:271–276

    Article  PubMed  CAS  Google Scholar 

  • Krishnan V, Nestler EJ (2008) The molecular neurobiology of depression. Nature 455:894–902

    Article  PubMed  CAS  Google Scholar 

  • Lima L, Cubillos S (1998) Taurine might be acting as a trophic factor in the retina by modulating phosphorylation of cellular proteins. J Neurosci Res 53:377–384

    Article  PubMed  CAS  Google Scholar 

  • Lutter M, Krishnan V, Russo SJ, Jung S, McClung CA, Nestler EJ (2008) Orexin signaling mediates the antidepressant-like effect of calorie restriction. J Neurosci 28:3071–3075

    Article  PubMed  CAS  Google Scholar 

  • Miyakawa T, Leiter LM, Gerber DJ, Gainetdinov RR, Sotnikova TD, Zeng H, Caron MG, Tonegawa S (2003) Conditional calcineurin knockout mice exhibit multiple abnormal behaviors related to schizophrenia. Proc Natl Acad Sci USA 100:8987–8992

    Article  PubMed  CAS  Google Scholar 

  • Miyazaki T, Matsuzaki Y, Ikegami T, Miyakawa S, Doy M, Tanaka N, Bouscarel B (2004) Optimal and effective oral dose of taurine to prolong exercise performance in rat. Amino Acids 27:291–298

    Article  PubMed  CAS  Google Scholar 

  • Murakami T, Furuse M (2010) The impact of taurine- and beta-alanine-supplemented diets on behavioral and neurochemical parameters in mice: antidepressant versus anxiolytic-like effects. Amino Acids 39:427–434

    Article  PubMed  CAS  Google Scholar 

  • Murakami T, Yamane H, Tomonaga S, Furuse M (2009) Forced swimming and imipramine modify plasma and brain amino acid concentrations in mice. Eur J Pharmacol 602:73–77

    Article  PubMed  CAS  Google Scholar 

  • Perry TL, Bratty PJ, Hansen S, Kennedy J, Urquhart N, Dolman CL (1975) Hereditary mental depression and Parkinsonism with taurine deficiency. Arch Neurol 32:108–113

    Article  PubMed  CAS  Google Scholar 

  • Qi X, Lin W, Li J, Pan Y, Wang W (2006) The depressive-like behaviors are correlated with decreased phosphorylation of mitogen-activated protein kinases in rat brain following chronic forced swim stress. Behav Brain Res 175:233–240

    Article  PubMed  CAS  Google Scholar 

  • Sergeeva OA, Chepkova AN, Doreulee N, Eriksson KS, Poelchen W, Mönnighoff I, Heller-Stilb B, Warskulat U, Häussinger D, Haas HL (2003) Taurine-induced long-lasting enhancement of synaptic transmission in mice: role of transporters. J Physiol 550:911–919

    Article  PubMed  CAS  Google Scholar 

  • Shirayama Y, Chen AC, Nakagawa S, Russell DS, Duman RS (2002) Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. J Neurosci 22:3251–3261

    PubMed  CAS  Google Scholar 

  • Silva AJ, Paylor R, Wehner JM, Tonegawa S (1992a) Impaired spatial learning in alpha-calcium-calmodulin kinase II mutant mice. Science 257:206–211

    Article  PubMed  CAS  Google Scholar 

  • Silva AJ, Stevens CF, Tonegawa S, Wang Y (1992b) Deficient hippocampal long-term potentiation in alpha-calcium-calmodulin kinase II mutant mice. Science 257:201–206

    Article  PubMed  CAS  Google Scholar 

  • Suárez LM, Solís JM (2006) Taurine potentiates presynaptic NMDA receptors in hippocampal Schaffer collateral axons. Eur J Neurosci 24:405–418

    Article  PubMed  Google Scholar 

  • Takao K, Tanda K, Nakamura K, Kasahara J, Nakao K, Katsuki M, Nakanishi K, Yamasaki N, Toyama K, Adachi M, Umeda M, Araki T, Fukunaga K, Kondo H, Sakagami H, Miyakawa T (2010) Comprehensive behavioral analysis of calcium/calmodulin-dependent protein kinase IV knockout mice. PLoS One 5:e9460

    Article  PubMed  Google Scholar 

  • Tamai I, Senmaru M, Terasaki T, Tsuji A (1995) Na(+)- and Cl(-)-dependent transport of taurine at the blood-brain barrier. Biochem Pharmacol 50:1783–1793

    Article  PubMed  CAS  Google Scholar 

  • Tanabe M, Nitta A, Ono H (2010) Neuroprotection via strychnine-sensitive glycine receptors ­during post-ischemic recovery of excitatory synaptic transmission in the hippocampus. J Pharmacol Sci 113:378–386

    Article  PubMed  CAS  Google Scholar 

  • Timbrell JA, Seabra V, Waterfield CJ (1995) The in vivo and in vitro protective properties of ­taurine. Gen Pharmacol 26:453–462

    Article  PubMed  CAS  Google Scholar 

  • Tiraboschi E, Giambelli R, D’Urso G, Galietta A, Barbon A, de Bartolomeis A, Gennarelli M, Barlati S, Racagni G, Popoli M (2004) Antidepressants activate CaMKII in neuron cell body by Thr286 phosphorylation. Neuroreport 15:2393–2396

    Article  PubMed  CAS  Google Scholar 

  • Tomida S, Mamiya T, Sakamaki H, Miura M, Aosaki T, Masuda M, Niwa M, Kameyama T, Kobayashi J, Iwaki Y, Imai S, Ishikawa A, Abe K, Yoshimura T, Nabeshima T, Ebihara S (2009) Usp46 is a quantitative trait gene regulating mouse immobile behavior in the tail ­suspension and forced swimming tests. Nat Genet 41:688–695

    Article  PubMed  CAS  Google Scholar 

  • Tsankova NM, Berton O, Renthal W, Kumar A, Neve RL, Nestler EJ (2006) Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action. Nat Neurosci 9:519–525

    Article  PubMed  CAS  Google Scholar 

  • Vaswani M, Linda FK, Ramesh S (2003) Role of selective serotonin reuptake inhibitors in psychiatric disorders: a comprehensive review. Prog Neuropsychopharmacol Biol Psychiatry 27: 85–102

    Article  PubMed  CAS  Google Scholar 

  • Whirley BK, Einat H (2008) Taurine trials in animal models offer no support for anxiolytic, antidepressant or stimulant effects. Isr J Psychiatry Relat Sci 45:11–18

    PubMed  Google Scholar 

  • Whittle N, Sartori SB, Dierssen M, Lubec G, Singewald N (2007) Fetal Down syndrome brains exhibit aberrant levels of neurotransmitters critical for normal brain development. Pediatrics 120:e1465–e1471

    Article  PubMed  Google Scholar 

  • Wong PT, Ong YP (2001) Acute antidepressant-like and antianxiety-like effects of tryptophan in mice. Pharmacology 62:151–156

    Article  PubMed  CAS  Google Scholar 

  • Wu JY, Prentice H (2010) Role of taurine in the central nervous system. J Biomed Sci 17(Suppl 1):S1

    Article  PubMed  Google Scholar 

  • Xing G, Russell S, Hough C, O’Grady J, Zhang L, Yang S, Zhang LX, Post R (2002) Decreased prefrontal CaMKII alpha mRNA in bipolar illness. Neuroreport 13:501–505

    Article  PubMed  CAS  Google Scholar 

  • Yamasaki N, Maekawa M, Kobayashi K, Kajii Y, Maeda J, Soma M, Takao K, Tanda K, Ohira K, Toyama K, Kanzaki K, Fukunaga K, Sudo Y, Ichinose H, Ikeda M, Iwata N, Ozaki N, Suzuki H, Higuchi M, Suhara T, Yuasa S, Miyakawa T (2008) Alpha-CaMKII deficiency causes immature dentate gyrus, a novel candidate endophenotype of psychiatric disorders. Mol Brain 1:6

    Article  PubMed  Google Scholar 

  • Yatabe Y, Miyakawa S, Miyazaki T, Matsuzaki Y, Ochiai N (2003) Effects of taurine administration in rat skeletal muscles on exercise. J Orthop Sci 8:415–419

    Article  PubMed  CAS  Google Scholar 

  • Zheng WH, Quirion R (2004) Comparative signaling pathways of insulin-like growth factor-1 and brain-derived neurotrophic factor in hippocampal neurons and the role of the PI3 kinase pathway in cell survival. J Neurochem 89:844–852

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Dr. Hiroko Toyoda (Ibaraki University) for helpful comments regarding the manuscript. Also we thank Dr. Mitsuhiro Furuse and Dr. Shozo Tomonaga (Kyushu University) for fruitful discussion of this study. This research was supported in part by Grants-in-Aid for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Author information

Authors and Affiliations

  1. College of Agriculture, Ibaraki University, Ami, Ibaraki, 300-0393, Japan

    Atsushi Toyoda & Wataru Iio

  2. United Graduate School of Agricultural Science, Tokyo University of Agriculture and Technology, Fuchu-city, Tokyo, 183-8509, Japan

    Atsushi Toyoda & Wataru Iio

Authors
  1. Atsushi Toyoda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wataru Iio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Atsushi Toyoda .

Editor information

Editors and Affiliations

  1. City University of New York, Center for Developmental Neuroscience, College of Staten Island, 2800 Victory Blvd, Staten Island, 10314, New York, USA

    Abdeslem El Idrissi

  2. City University of New York, Department of Biology, College of Staten Island, Victory Blvd 2800, Staten Island, 10314, New York, USA

    William J. L'Amoreaux

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this paper

Cite this paper

Toyoda, A., Iio, W. (2013). Antidepressant-Like Effect of Chronic Taurine Administration and Its Hippocampal Signal Transduction in Rats. In: El Idrissi, A., L'Amoreaux, W. (eds) Taurine 8. Advances in Experimental Medicine and Biology, vol 775. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6130-2_3

Download citation

Publish with us

Policies and ethics

Search

Navigation