Skip to main content
SpringerLink
Log in

Hypothesis with abnormal amino acid metabolism in depression and stress vulnerability in Wistar Kyoto rats

  • Original Article
  • Published:
Amino Acids Aims and scope Submit manuscript

Abstract

While abnormalities in monoamine metabolism have been investigated heavily per potential roles in the mechanisms of depression, the contribution of amino acid metabolism in the brain remains not well understood. In additional, roles of the hypothalamus–pituitary–adrenal axis in stress-regulation mechanisms have been of much focus, while the contribution of central amino acid metabolism to these mechanisms has not been well appreciated. Therefore, whether depression-like states affect amino acid metabolism and their potential roles on stress-regulatory mechanisms were investigated by comparing Wistar Kyoto rats, which display depression-like behaviors and stress vulnerability, to control Wistar rats. Brain amino acid metabolism in Wistar Kyoto rats was greatly different from normal Wistar rats, with special reference to lower cystathionine and serine levels. In addition, Wistar Kyoto rats demonstrated abnormality in dopamine metabolism compared with Wistar rats. In the case of stress response, amino acid levels having a sedative and/or hypnotic effect were constant in the brain of Wistar Kyoto rats, though these amino acid levels were reduced in Wistar rats under a stressful condition. These results suggest that the abnormal amino acid metabolism may induce depression-like behaviors and stress vulnerability in Wistar Kyoto rats. Therefore, we hypothesized that abnormalities in amino acid and monoamine metabolism may induce depression, and amino acid metabolism in the brain may be related to stress vulnerability.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Aitken SM, Lodha PH, Morneau JK (2011) The enzymes of the transfiguration pathway: active-site characterizations. Biochim Biophys Acta 1814:1511–1517

    Article  PubMed  CAS  Google Scholar 

  • Asechi M, Tomonaga S, Tachibana T, Han L, Hayamizu K, Denbow DM, Furuse M (2006) Intracerebroventricular injection of l-serine analogs and derivatives induces sedative and hypnotic effects under an acute stressful condition in neonatal chicks. Behav Brain Res 170:71–77

    Article  PubMed  CAS  Google Scholar 

  • Coppen A (1967) The biochemistry of affective disorder. Br J Psychiatry 113:1237–1264

    Article  PubMed  CAS  Google Scholar 

  • De La Garza R, Mahoney JJ (2004) A distinct neurochemical profile in WKY rats at baseline and in response to acute stress: implications for animal model of anxiety and depression. Brain Res 1021:209–218

    Article  Google Scholar 

  • Elizalde N, Gil-Bea FJ, Ramírez MJ, Aisa B, Lasheras B, Del Rio J, Tordera RM (2008) Long-lasting behavioral effects and recognition memory deficit induced by chronic mild stress in mice: effect of antidepressant treatment. Psychopharmacology 199:1–14

    Article  PubMed  CAS  Google Scholar 

  • Gamaro GD, Manoli LP, Torres ILS, Silveira R, Dalmaz C (2003) Effects of chronic variate stress on feeding behavior and on monoamine levels in different rat brain structure. Neurochem Int 42:107–114

    Article  PubMed  CAS  Google Scholar 

  • Hamasu K, Haraguchi T, Kabuki Y, Adachi N, Tomonaga S, Sato H, Denbow M, Furuse M (2009) l-proline is a sedative regulator of acute stress in the brain of neonatal chicks. Amino Acids 37:377–382

    Article  PubMed  CAS  Google Scholar 

  • Hamasu K, Shigemi K, Tsuneyoshi Y, Yamane H, Sato H, Denbow M, Furuse M (2010) Intracerebroventricular injection of l-proline and d-proline induces sedative and hypnotic effects by different mechanisms under an acute stressful condition in chicks. Amino Acids 38:57–64

    Article  PubMed  CAS  Google Scholar 

  • Hauge ER, Berle JQ, Oedegaard KJ, Holsten F, Fasmer OB (2011) Nonlinear analysis of motor activity shows differences between schizophrenia and depression: a study using Fourier analysis and sample entropy. PLoS ONE 6:e16291

    Article  PubMed  CAS  Google Scholar 

  • Jiao X, Paré WP, Tejani-Butt SM (2006) Alcohol consumption alters dopamine transporter sites in Wistar-Kyoto rat brain. Brain Res 1073–1074:175–182

    Article  PubMed  Google Scholar 

  • Kabuki Y, Mizobe Y, Yamada S, Furuse M (2009) Dietary l-tyrosine alleviates the behavioral alterations induced by social isolation stress in mice. Brain Res Bull 80:389–396

    Article  PubMed  CAS  Google Scholar 

  • Kokras N, Antoniou K, Polissidis A, Papadopoulou-Daifoti Z (2009) Antidepressants induce regionally discrete, sex-dependent changes in brain’s glutamate content. Neurosci Lett 464:98–102

    Article  PubMed  CAS  Google Scholar 

  • Kurata K, Shigemi K, Tomonaga S, Aoki M, Morishita K, Denbow DM, Furuse M (2011) l-Ornithine attenuates corticotropin-releasing factor-induced stress responses acting at GABAA receptors in neonatal chicks. Neuroscience 172:226–231

    Article  PubMed  CAS  Google Scholar 

  • Kurauchi I, Asechi M, Tachibana T, Han L, Hayamizu K, Denbow DM, Furuse M (2006) Intracerebroventricular injection of l-alanine induces a sedative effect under an acute stressful condition in neonatal chicks. J Poult Sci 43:384–387

    Article  CAS  Google Scholar 

  • Lahmame A, Armario A (1996) Differential responsiveness of inbred starins of rats to antidepressants in the forced swimming: are Wistar-Kyoto rats an animal model of subsensitively to antidepressant? Psychopharmacology 123:191–198

    Article  PubMed  CAS  Google Scholar 

  • Lanni C, Govoni S, Lucchelli A, Boselli C (2009) Depression and antidepressants: molecular and cellular aspects. Cell Mol Life Sci 66:2985–3008

    Article  PubMed  CAS  Google Scholar 

  • Lee ESY, Chen H, Soliman KFA, Charlton CG (2005) Effects of homocysteine on the dopaminergic system and behavior in rodents. Neurotoxicology 26:361–371

    Article  PubMed  CAS  Google Scholar 

  • López-Rubalcava C, Lucki I (2000) Strain differences in the behavioral effects of antidepressant drugs in the rat forced swimming test. Neuropsychopharmacology 22:191–199

    Article  PubMed  Google Scholar 

  • Lucca G, Comin CM, Valvassori S, Re′us GZ, Vuolo F, Petronilho F, Dal-Pizzol F, Gavioli EC, Quevedo J (2009) Effects of chronic mild stress on the oxidative parameters in the rat brain. Neurochem Int 54:358–362

    Article  PubMed  CAS  Google Scholar 

  • Malkesman O, Austin DR, Tragon T, Wang G, Rompala G, Hamidi AB, Cui Z, Young WS, Nakazawa K, Zarate Jr CA, Manji HK, Chen G (2011) Acute d-serine treatment produces antidepressant-like effects in rodents. Int J Neuropsychopharmacol (in press)

  • Matte′ C, Mackedanz V, Stefanello FM, Scherer EBS, Andreazza AC, Zanotto C, Moro AM, Garcia SC, Gonc alves CA, Erdtmann B, Salvador M, Wyse ATS (2009) Chronic hyperhomocysteinemia alters antioxidant defenses and increases DNA damage in brain and blood of rats: protective effect of folic acid. Neurochem Int 54:7–13

    Article  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 T, 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 

  • Ng F, Berk M, Dean O, Bush A (2008) Oxidative stress in psychiatric disorders: evidence base and therapeutic implications. Int J Neuropsychopharmacol 11:851–876

    Article  PubMed  CAS  Google Scholar 

  • O’Mahony CM, Clarke G, Gibney S, Dinan TG, Cryan JF (2011) Strain differences in the neurochemical response to chronic restraint stress in the rat: relevance to depression. Pharmacol Biochem Behav 97:690–699

    Article  PubMed  Google Scholar 

  • Pare′ WP (1990) Technique and strain comparisons in stress ulcer. Ann N Y Acad Sci 597:223–230

    Article  Google Scholar 

  • Pare′ WP (1994) Open field, learned helplessness, conditioned defensive burying, and forced-swim tests in WKY rats. Physiol Behav 55:433–439

    Article  Google Scholar 

  • Pincus HA, Pettit AR (2001) The societal costs of chronic major depression. J Clin Psychiatry 62:5–9

    PubMed  Google Scholar 

  • Porsolt RD, Anton G, Blavet N, Jalfre M (1978) Behavioral despair in rats: a new model sensitive to antidepressant treatment. Eur J Pharmacol 47:379–391

    Article  PubMed  CAS  Google Scholar 

  • Suenaga R, Tomonaga S, Yamane H, Kurauchi I, Tsuneyoshi Y, Sato H, Denbow DM, Furuse M (2008) Intracerebroventricular injection of l-arginine induces sedative and hypnotic effects under an acute stressful condition in neonatal chicks. Amino Acids 35:139–146

    Article  PubMed  CAS  Google Scholar 

  • Tagliari B, Dos Santos TM, Cunha AA, Lima DD, Delwing D, Sitta A, Vargas CR, Dalmaz C (2010) Chronic variable stress induces oxidative stress and decreases butyrylcholinesterase activity in blood of rats. J Neural Transm 117:1067–1076

    Article  PubMed  CAS  Google Scholar 

  • Takagi T, Ando R, Ohgushi A, Yamashita T, Dobashi E, Hussain-Yusuf H, Onodera R, Bungo T, Sato H, Furuse M (2001) Intracerebroventricular injection of pipecolic acid inhibits food intake and induces sleeping-like behaviors in the neonatal chick. Neurosci Lett 310:97–100

    Article  PubMed  CAS  Google Scholar 

  • Takasugi Y, Kawata K, Okura T, Koga Y, Mizuguchi N, Yamanaka S, Watanabe S (2003) Strain differences to effects of aging on concentrations of amino acids in cerebrospinal fluid between Sprague Dawley and Wistar Kyoto rats. Exp Anim 52:429–432

    Article  PubMed  CAS  Google Scholar 

  • Tejani-Butt S, Kluczynski J, Pare′ WP (2003) Strain-dependent modification of behavior following antidepressant treatment. Prog Neuropsychopharmacol Biol Pshchiatry 27:7–14

    Article  CAS  Google Scholar 

  • World Health Organization (2004) Disease and Injury Regional estimates for 2004. http://www.who.int/healthinfo/global_burden_disease/estimates_regional/en/index.html. Accessed 3 January 2012

  • Yamada H, Akahoshi N, Kamata S, Hagiya Y, Hishiki T, NagahataY, Matsuura T, Takano N, Mori M, Ishizaki Y, Izumi T, Kumagai Y, Kasahara T, Suematsu M, Ishii I (2012) Methionine excess in diet induce acute lethal hepatitis in mice lacking cystathionine γ-lyase, an animal model of cystathioninuria. Free Radic Biol Med (in press)

  • Yamane H, Asechi M, Tsuneyoshi Y, Kurauchi I, Denbow DM, Furuse M (2009) Intracerebroventricular injection of l-aspartic acid and l-asparagine induces sedative effects under an acute stressful condition in neonatal chicks. Anim Sci J 80:286–290

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors are grateful to the staff and students of the Laboratory of Chemistry and Technology of Animal Products in Kyushu University for their assistance in the amino acid analysis. This work was supported by a Grant-in-Aid for Scientific Research (No. 23248046 to MF) from the Japan Society for the Promotion of Science. A part of present study was supported by Kieikai Research Foundation.

Author information

Authors and Affiliations

  1. Laboratory of Regulation in Metabolism and Behavior, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka, 812-8581, Japan

    Mao Nagasawa, Yumi Ogino, Koji Kurata, Tsuyoshi Otsuka, Jyunki Yoshida, Shozo Tomonaga & Mitsuhiro Furuse

Authors
  1. Mao Nagasawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yumi Ogino
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Koji Kurata
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tsuyoshi Otsuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jyunki Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shozo Tomonaga
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mitsuhiro Furuse
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mitsuhiro Furuse.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nagasawa, M., Ogino, Y., Kurata, K. et al. Hypothesis with abnormal amino acid metabolism in depression and stress vulnerability in Wistar Kyoto rats. Amino Acids 43, 2101–2111 (2012). https://doi.org/10.1007/s00726-012-1294-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-012-1294-y

Keywords

Search

Navigation