Korean J Physiol Pharmacol.  2014 Oct;18(5):371-376. 10.4196/kjpp.2014.18.5.371.

Alterations of Amino Acid Level in Depressed Rat Brain

Affiliations
  • 1School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, P.R. China 100029. njtcm@263.net

Abstract

Amino-acid neurotransmitter system dysfunction plays a major role in the pathophysiology of depression. Several studies have demonstrated the potential of amino acids as a source of neuro-specific biomarkers could be used in future diagnosis of depression. Only partial amino acids such as glycine and asparagine were determined from certain parts of rats' brain included hippocampi and cerebral cortex in previous studies. However, according to systematic biology, amino acids in different area of brain are interacted and interrelated. Hence, the determination of 34 amino acids through entire rats' brain was conducted in this study in order to demonstrate more possibilities for biomarkers of depression by discovering other potential amino acids in more areas of rats' brain. As a result, 4 amino acids (L-aspartic acid, L-glutamine, taurine and gamma-amino-n-butyric acid) among 34 were typically identified as potentially primary biomarkers of depression by data statistics. Meanwhile, an antidepressant called Fluoxetine was employed to verify other potential amino acids which were not identified by data statistics. Eventually, we found L-alpha-amino-adipic acid could also become a new potentially secondary biomarker of depression after drug validation. In conclusion, we suggested that L-aspartic acid, L-glutamine, taurine, gamma-amino-n-butyric acid and L-alpha-amino-adipic acid might become potential biomarkers for future diagnosis of depression and development of antidepressant.

Keyword

Amino acids; Behavior; Chronic Unpredictable Mild Stress; Depression; LC-MS/MS

MeSH Terms

Amino Acids
Animals
Asparagine
Aspartic Acid
Biomarkers
Biology
Brain*
Cerebral Cortex
Depression
Diagnosis
Fluoxetine
Glutamine
Glycine
Neurotransmitter Agents
Rats*
Taurine
Amino Acids
Asparagine
Aspartic Acid
Fluoxetine
Glutamine
Glycine
Neurotransmitter Agents
Taurine

Figure

  • Fig. 1 Total Ion Chromatography of amino acids.

  • Fig. 2 Scores and loadings from PCA and PLS-DA.


Reference

1. Keck ME. Corticotropin-releasing factor, vasopressin and receptor systems in depression and anxiety. Amino Acids. 2006; 31:241–250. PMID: 16733617.
Article
2. Frazer A, Morilak DA. What should animal models of depression model? Neurosci Biobehav Rev. 2005; 29:515–523. PMID: 15893377.
Article
3. Katz RJ. Animal model of depression: effects of electroconvulsive shock therapy. Neurosci Biobehav Rev. 1981; 5:273–277. PMID: 7196558.
Article
4. Katz RJ. Animal model of depression: pharmacological sensitivity of a hedonic deficit. Pharmacol Biochem Behav. 1982; 16:965–968. PMID: 7202217.
Article
5. Katz RJ, Baldrighi G. A further parametric study of imipramine in an animal model of depression. Pharmacol Biochem Behav. 1982; 16:969–972. PMID: 7202218.
Article
6. Yoon SH, Kim BH, Ye SK, Kim MH. Chronic non-social stress affects depressive behaviors but not anxiety in mice. Korean J Physiol Pharmacol. 2014; 18:263–268. PMID: 24976767.
Article
7. Bennett GS, Edelman GM. Amino acid incorporation into rat brain proteins during spreading cortical depression. Science. 1969; 163:393–395. PMID: 5762776.
Article
8. Johnson ES, Roberts MH, Straughan DW. Amino-acid induced depression of cortical neurones. Br J Pharmacol. 1970; 38:659–666. PMID: 5445689.
Article
9. Farkas T, Dunner DL, Fieve RR. L-tryptophan in depression. Biol Psychiatry. 1976; 11:295–302. PMID: 779855.
10. Branchey L, Branchey M, Shaw S, Lieber CS. Relationship between changes in plasma amino acids and depression in alcoholic patients. Am J Psychiatry. 1984; 141:1212–1215. PMID: 6486254.
11. Jang HJ, Cho KH, Park SW, Kim MJ, Yoon SH, Rhie DJ. Effects of serotonin on the induction of long-term depression in the rat visual cortex. Korean J Physiol Pharmacol. 2010; 14:337–343. PMID: 21165334.
Article
12. Bellodi L, Erzegovesi S, Bianchi L, Lucini V, Conca R, Lucca A. Plasma tryptophan levels and tryptophan/neutral amino acid ratios in obsessive-compulsive patients with and without depression. Psychiatry Res. 1997; 69:9–15. PMID: 9080540.
Article
13. Pan Y, Hong Y, Zhang QY, Kong LD. Impaired hypothalamic insulin signaling in CUMS rats: restored by icariin and fluoxetine through inhibiting CRF system. Psychoneuroendocrinology. 2013; 38:122–134. PMID: 22663897.
Article
14. Li Y, Xu LL, Ruan JX, Zhang ZQ. Research progress of enhancing quantitative sensitivity by using LC-MS(n) with derivatization method in bio-matrices. Yao Xue Xue Bao. 2011; 46:637–641. PMID: 21882522.
15. Küçükibrahimoğlu E, Saygin MZ, Calişkan M, Kaplan OK, Unsal C, Gören MZ. The change in plasma GABA, glutamine and glutamate levels in fluoxetine- or S-citalopram-treated female patients with major depression. Eur J Clin Pharmacol. 2009; 65:571–577. PMID: 19373461.
Article
16. McEwen AM, Burgess DT, Hanstock CC, Seres P, Khalili P, Newman SC, Baker GB, Mitchell ND, Khudabux-Der J, Allen PS, LeMelledo JM. Increased glutamate levels in the medial prefrontal cortex in patients with postpartum depression. Neuropsychopharmacology. 2012; 37:2428–2435. PMID: 22805604.
Article
17. Haas HL, Hösli L. The depression of brain stem neurones by taurine and its interaction with strychnine and bicuculline. Brain Res. 1973; 52:399–402. PMID: 4700718.
Article
18. Toyoda A, Iio W. Antidepressant-like effect of chronic taurine administration and its hippocampal signal transduction in rats. Adv Exp Med Biol. 2013; 775:29–43. PMID: 23392922.
Article
19. Bellance N, Pabst L, Allen G, Rossignol R, Nagrath D. Oncosecretomics coupled to bioenergetics identifies alpha-amino adipic acid, isoleucine and GABA as potential biomarkers of cancer: Differential expression of c-Myc, Oct1 and KLF4 coordinates metabolic changes. Biochim Biophys Acta. 2012; 1817:2060–2071. PMID: 22842522.
20. Gelenberg AJ, Wurtman RJ. L-tyrosine in depression. Lancet. 1980; 2:863–864. PMID: 6107536.
Article
21. Goldberg IK. L-tyrosine in depression. Lancet. 1980; 2:364–365. PMID: 6105492.
Article
22. Hoskins JA. L-tyrosine in depression. Lancet. 1980; 2:597. PMID: 6106779.
Article
23. Mouret J, Lemoine P, Minuit MP, Robelin N. L-tyrosine cures, immediate and long term, dopamine-dependent depressions. Clinical and polygraphic studies. C R Acad Sci III. 1988; 306:93–98. PMID: 3126995.
24. Nagasawa M, Ogino Y, Kurata K, Otsuka T, Yoshida J, Tomonaga S, Furuse M. Hypothesis with abnormal amino acid metabolism in depression and stress vulnerability in Wistar Kyoto rats. Amino Acids. 2012; 43:2101–2111. PMID: 22526244.
Article
Full Text Links
  • KJPP
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr