Advertisement

Neurotoxicity Research

, Volume 34, Issue 3, pp 375–387 | Cite as

L-Theanine Decreases Orofacial Dyskinesia Induced by Reserpine in Rats

  • Hung-Sheng Soung
  • Mao-Hsien Wang
  • Kuo-Chi Chang
  • Cheng-Neng Chen
  • Yi Chang
  • Chih-Chuan Yang
  • Hsiang-Chien Tseng
ORIGINAL ARTICLE
  • 50 Downloads

Abstract

Reserpine (RES)-induced orofacial dyskinesia (OD) has been used as an animal model for human tardive dyskinesia (TD) for decades, due to its strong pathophysiological association with striatal oxidative stress and neural cytoarchitecture alteration. L-Theanine (LT), one of the major amino acid components in green tea, has potent antioxidative, anti-inflammatory, and neuroprotective effects. In this study, we examined the potential protective effects of LT on RES-induced behavioral and neurochemical dysfunction in rats. RES treatment (1 mg/kg s.c., 3 injections 1 day apart) induced significant increases (p < 0.001) in the frequency of vacuous chewing movements (VCM), tongue protrusion (TP), as well as the duration of facial twitching (FT). LT treatment (100, 300 mg/kg orally for 14 days, starting 10 days before RES injection) was able to prevent most of the RES-induced OD. Moreover, LT treatment reduced the RES-induced lipid peroxidation (LPO) production, increased the antioxidation power and catecholamines in the striatum, and significantly reduced the levels of neuroinflammatory and apoptotic markers. Our results indicated that LT was able to counteract the increased oxidative damage, neurotransmitter deficiency, neuroinflammation, and apoptosis induced by RES, and these results have demonstrated the possible neuroprotective effects of LT against RES-induced OD, including antioxidation, neurochemical deficiency prevention, antineuroinflammation, and antiapoptosis. These findings, therefore, suggest a potential role for LT to have a clinically relevant therapeutic effect in delaying or treating human TD.

Keywords

L-Theanine Orofacial dyskinesia Reserpine Striatum 

Abbreviations

CAT

catalase

DA

dopamine

FT

facial twitching

GSH

glutathione

IL-6

interleukin-6

LPO

lipid peroxidation

MAO

monoamine oxidase

NE

norepinephrine

OD

orofacial dyskinesia

PD

Parkinson disease

RES

reserpine

SOD

superoxide dismutase

LT

L-theanine

TBARS

thiobarbituric acid-reactive substance

TD

tardive dyskinesia

TNF-α

tumor necrosis factor α

TP

tongue protrusion

VCM

vacuous chewing movements

VMAT

vesicular monoamine transporter

5-HT

serotonin

Notes

Acknowledgements

The authors thank Persistent BioMed Editing services located in Philadelphia, USA, for their valuable editing and proofreading of the current manuscript.

Funding Information

This study was supported by the Yuan-Shan Br. of Taipei Veteran General Hospital (YSVH-10505), Mackay Memorial Hospital (MMH-105-69), and Shin Kong Wu Ho-Su Memorial Hospital (SKH-8302-104-DR-24).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. Abílio VC, Silva RH, Carvalho RC, Grassl C, Calzavara MB, Registro S, D’Almeida V, Ribeiro Rde A, Frussa-Filho R (2004) Important role of striatal catalase in aging- and reserpine-induced oral dyskinesia. Neuropharmacology 47(2):263–272CrossRefGoogle Scholar
  2. Andreassen OA, Ferrante RJ, Beal MF, Jørgensen HA (1998) Oral dyskinesias and striatal lesions in rats after long-term co-treatment with haloperidol and 3-nitropropionic acid. Neuroscience 87(3):639–648CrossRefGoogle Scholar
  3. Beers RF Jr, Sizer IW (1952) A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem 195(1):133–140PubMedGoogle Scholar
  4. Bilska A, Dubiel M, Sokołowska-Jezewicz M, Lorenc-Koci E, Włodek L (2007) Alpha-lipoic acid differently affects the reserpine-induced oxidative stress in the striatum and prefrontal cortex of rat brain. Neuroscience 146(4):1758–1771CrossRefGoogle Scholar
  5. Burger ME, Alves A, Callegari L, Athayde FR, Nogueira CW, Zeni G, Rocha JB (2003) Ebselen attenuates reserpine-induced orofacial dyskinesia and oxidative stress in rat striatum. Prog Neuro-Psychopharmacol Biol Psychiatry 27(1):135–140CrossRefGoogle Scholar
  6. Calvente PR, Araujo CC, Bergamo M, Abilio VC, D’Almeida V, Ribeiro Rde A, Frussa FR (2002) The mitochondrial toxin 3-nitropropionic acid aggravates reserpine-induced oral dyskinesia in rats. Prog Neuro-Psychopharmacol Biol Psychiatry 26(2):401–405CrossRefGoogle Scholar
  7. Cunha AS, Matheus FC, Moretti M, Sampaio TB, Poli A, Santos DB, Colle D, Cunha MP, Blum-Silva CH, Sandjo LP, Reginatto FH, Rodrigues AL, Farina M, Prediger RD (2016) Agmatine attenuates reserpine-induced oral dyskinesia in mice: role of oxidative stress, nitric oxide and glutamate NMDA receptors. Behav Brain Res 312:64–76CrossRefGoogle Scholar
  8. Datta S, Jamwal S, Deshmukh R, Kumar P (2016) Beneficial effects of lycopene against haloperidol induced orofacial dyskinesia in rats: possible neurotransmitters and neuroinflammation modulation. Eur J Pharmacol 771:229–235CrossRefGoogle Scholar
  9. Davies DL, Shepherd M (1955) Reserpine in the treatment of anxious and depressed patients. Lancet 269(6881):117–120CrossRefGoogle Scholar
  10. de Freitas CM, Busanello A, Schaffer LF, Peroza LR, Krum BN, Leal CQ, Ceretta AP, da Rocha JB, Fachinetto R (2016) Behavioral and neurochemical effects induced by reserpine in mice. Psychopharmacology 233(3):457–467CrossRefGoogle Scholar
  11. Durlach J (1956) Treatment of emaciation with reserpine. Concours Med 78(7):725–728PubMedGoogle Scholar
  12. Dutra RC, Andreazza AP, Andreatini R, Tufik S, Vital MA (2002) Behavioral effects of MK-801 on reserpine-treated mice. Prog Neuro-Psychopharmacol Biol Psychiatry 26(3):487–495CrossRefGoogle Scholar
  13. Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82(1):70–77CrossRefGoogle Scholar
  14. Faria RR, Abílio VC, Grassl C, Chinen CC, Negrão LT, de Castro JP, Fukushiro DF, Rodrigues MS, Gomes PH, Registro S, de Carvalho Rde C, D’Almeida V, Silva RH, Ribeiro Rde A, Frussa-Filho R (2005) Beneficial effects of vitamin C and vitamin E on reserpine-induced oral dyskinesia in rats: critical role of striatal catalase activity. Neuropharmacology 48(7):993–1001CrossRefGoogle Scholar
  15. Fernandes VS, Santos JR, Leão AH, Medeiros AM, Melo TG, Izídio GS, Cabral A, Ribeiro RA, Abílio VC, Ribeiro AM, Silva RH (2012) Repeated treatment with a low dose of reserpine as a progressive model of Parkinson’s disease. Behav Brain Res 231(1):154–163CrossRefGoogle Scholar
  16. Fuentes P, Paris I, Nassif M, Caviedes P, Segura-Aguilar J (2007) Inhibition of VMAT- 2 and DT-diaphorase induced cell death in a substantia nigra-derived cell line—an experimental cell model for dopamine toxicity studies. Chem Res Toxicol 20(5):776–783CrossRefGoogle Scholar
  17. Hanff TC, Furst SJ, Minor TR (2010) Biochemical and anatomical substrates of depression and sickness behavior. J Psychiatry Relat Sci 47(1):64–71Google Scholar
  18. Hashimoto M, Tanabe Y, Fujii Y, Kikuta T, Shibata H, Shido O (2005) Chronic administration of docosahexaenoic acid ameliorates the impairment of spatial cognition learning ability in amyloid beta-infused rats. J Nutr 135(3):549–555CrossRefGoogle Scholar
  19. Huang NY, Kostrzewa RM, Li C, Perry KW, Fuller RW (1997) Persistent spontaneous oral dyskinesias in haloperidol-withdrawn rats neonatally lesioned with 6-hydroxydopamine: absence of an association with the Bmax for [3H]raclopride binding to neostriatal homogenates. J Pharmacol Exp Ther 280(1):268–276PubMedGoogle Scholar
  20. Ishibashi T, Ohno Y (2004) Antiparkinsonian actions of a selective 5-HT1A agonist, tandospirone, in rats. Biogen Amines 18:329–338CrossRefGoogle Scholar
  21. Jamwal S, Kumar P (2017) L-theanine, a component of green tea prevents 3-nitropropionic acid (3-NP)-induced striatal toxicity by modulating nitric oxide pathway. Mol Neurobiol 54(3):2327–2337CrossRefGoogle Scholar
  22. Kakuda T (2011) Neuroprotective effects of theanine and its preventive effects on cognitive dysfunction. Pharmacol Res 64(2):162–168CrossRefGoogle Scholar
  23. Kelley JJ, Roberts RC (2004) Effects of haloperidol on cholinergic striatal interneurons: relationship to oral dyskinesias. J Neural Transm 111(8):1075–1091CrossRefGoogle Scholar
  24. Kostrzewa RM, Huang NY, Kostrzewa JP, Nowak P, Brus R (2007) Modeling tardive dyskinesia: predictive 5-HT2C receptor antagonist treatment. Neurotox Res 11(1):41–50CrossRefGoogle Scholar
  25. Kronbauer M, Segat HJ, De David Antoniazzi CT, Roversi K, Roversi K, Pase CS, Barcelos RC, Burger ME (2015) Magnesium supplementation prevents and reverses experimentally induced movement disturbances in rats: biochemical and behavioral parameters. Biol Trace Elem Res 166(2):163–172CrossRefGoogle Scholar
  26. Kumar P, Kalonia H, Kumar A (2011) Role of LOX/COX pathways in 3-nitropropionic acid-induced Huntington’s disease-like symptoms in rats: protective effect of licofelone. Br J Pharmacol 164(2b):644–654CrossRefGoogle Scholar
  27. Lohr JB, Kuczenski R, Niculescu AB (2003) Oxidative mechanisms and tardive dyskinesia. CNS Drugs 17(1):47–62CrossRefGoogle Scholar
  28. Misra HP, Fridovich I (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247(10):3170–3175Google Scholar
  29. Nade VS, Shendye NV, Kawale LA, Patil NR, Khatri ML (2013) Protective effect of nebivolol on reserpine-induced neurobehavioral and biochemical alterations in rats. Neurochem Int 63(4):316–321CrossRefGoogle Scholar
  30. Naidu PS, Singh A, Kulkarni SK (2004) Reversal of reserpine-induced orofacial dyskinesia and cognitive dysfunction by quercetin. Pharmacology 70(2):59–67CrossRefGoogle Scholar
  31. Neisewander JL, Castañeda E, Davis DA (1994) Dose-dependent differences in the development of reserpine-induced oral dyskinesia in rats: support for a model of tardive dyskinesia. Psychopharmacology 116(1):79–84CrossRefGoogle Scholar
  32. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95(2):351–358CrossRefGoogle Scholar
  33. Paris I, Martinez-Alvarado P, Cárdenas S, Perez-Pastene C, Graumann R, Fuentes P, Olea-Azar C, Caviedes P, Segura-Aguilar J (2005) Dopamine-dependent iron toxicity in cells derived from rat hypothalamus. Chem Res Toxicol 18(3):415–419CrossRefGoogle Scholar
  34. Patel BA, Arundell M, Parker KH, Yeoman MS, O’Hare D (2005) Simple and rapid determination of serotonin and catecholamines in biological tissue using high-performance liquid chromatography with electrochemical detection. J Chromatogr B Analyt Technol Biomed Life Sci 818(2):269–276CrossRefGoogle Scholar
  35. Patil R, Dhawale K, Gound H, Gadakh R (2012a) Protective effect of leaves of Murraya koenigii on reserpine-induced orofacial dyskinesia. Iran J Pharm Res 11(2):635–641PubMedPubMedCentralGoogle Scholar
  36. Patil RA, Hiray YA, Kasture SB (2012b) Reversal of reserpine-induced orofacial dyskinesia and catalepsy by Nardostachys jatamansi. Indian J Pharmacol 44(3):340–344CrossRefGoogle Scholar
  37. Pérez-Vargas JE, Zarco N, Vergara P, Shibayama M, Segovia J, Tsutsumi V, Muriel P (2016) l-Theanine prevents carbon tetrachloride-induced liver fibrosis via inhibition of nuclear factor κB and down-regulation of transforming growth factor β and connective tissue growth factor. Hum Exp Toxicol 35(2):135–146CrossRefGoogle Scholar
  38. Santos JR, Cunha JA, Dierschnabel AL, Campêlo CL, Leão AH, Silva AF, Engelberth RC, Izídio GS, Cavalcante JS, Abílio VC, Ribeiro AM, Silva RH (2013) Cognitive, motor and tyrosine hydroxylase temporal impairment in a model of parkinsonism induced by reserpine. Behav Brain Res 253:68–77CrossRefGoogle Scholar
  39. Selvakumar G, Vijayraja D, Krishnamoorthy D, Manivasagam T (2012) Morin attenuates haloperidol induced tardive dyskinesia and oxidative stress in mice. J Nat Sci Res 8(2):153–165Google Scholar
  40. Sumathi T, Shobana C, Thangarajeswari M, Usha R (2015) Protective effect of L-theanine against aluminium induced neurotoxicity in cerebral cortex, hippocampus and cerebellum of rat brain—histopathological, and biochemical approach. Drug Chem Toxicol 38(1):22–231CrossRefGoogle Scholar
  41. Teixeira AM, Reckziegel P, Müller L, Pereira RP, Roos DH, Rocha JB, Bürger ME (2009) Intense exercise potentiates oxidative stress in striatum of reserpine-treated animals. Pharmacol Biochem Behav 92(2):231–235CrossRefGoogle Scholar
  42. Terashima T, Takido J, Yokogoshi H (1999) Time-dependent changes of amino acids in the serum, liver, brain and urine of rats administered with theanine. Biosci Biotechnol Biochem 63(4):615–618CrossRefGoogle Scholar
  43. Thangarajan S, Deivasigamani A, Natarajan SS, Krishnan P, Mohanan SK (2014) Neuroprotective activity of L-theanine on 3-nitropropionic acid-induced neurotoxicity in rat striatum. Int J Neurosci 124(9):673–684CrossRefGoogle Scholar
  44. Túnez I, Collado JA, Medina FJ, Peña J, Del C, Muñoz M, Jimena I, Franco F, Rueda I, Feijóo M, Muntané J, Montilla P (2006) 17 eta-Estradiol may affect vulnerability of striatum in a 3-nitropropionic acid-induced experimental model of Huntington’s disease in ovariectomized rats. Neurochem Int 48(5):367–373CrossRefGoogle Scholar
  45. Wang MH, Lin RF, Tseng HC, Soung HS, Chang KC, Tsai CC (2015) (−)Epigallocatechin-3-gallate attenuates reserpine-induced orofacial dyskinesia and oxidative stress in rat striatum. Pharmacol Biochem Behav 131:71–76CrossRefGoogle Scholar
  46. Yin C, Gou L, Liu Y, Yin X, Zhang L, Jia G, Zhuang X (2011) Antidepressant-like effects of L-theanine in the forced swim and tail suspension tests in mice. Phytother Res 25(11):1636–1639CrossRefGoogle Scholar
  47. Yokogoshi H, Kato Y, Sagesaka YM, Takihara-Matsuura T, Kakuda T, Takeuchi N (1995) Reduction effect of theanine on blood pressure and brain 5-hydroxyindoles in spontaneously hypertensive rats. Biosci Biotechnol Biochem 59(4):615–618CrossRefGoogle Scholar
  48. Zhang G, Miura Y, Yagasaki K (2002) Effects of dietary powdered green tea and theanine on tumor growth and endogenous hyperlipidemia in hepatoma-bearing rats. Biosci Biotechnol Biochem 66(4):711–716CrossRefGoogle Scholar
  49. Zheng G, Sayama K, Okubo T, Juneja LR, Oguni I (2004) Anti-obesity effects of three major components of green tea, catechins, caffeine and theanine, in mice. In Vivo 18(1):55–62PubMedGoogle Scholar
  50. Zukhurova M, Prosvirnina M, Daineko A, Simanenkova A, Petrishchev N, Sonin D, Galagudza M, Shamtsyan M, Juneja LR, Vlasov T (2013) L-theanine administration results in neuroprotection and prevents glutamate receptor agonist-mediated injury in the rat model of cerebral ischemia-reperfusion. Phytother Res 27(9):1282–1287CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PsychiatryYuan-Shan Br. of Taipei Veteran General HospitalYilan CountyRepublic of China
  2. 2.Department of AnesthesiaEn Chu Kon HospitalNew Taipei CityRepublic of China
  3. 3.Department of Chemical Engineering and BiotechnologyNational Taipei University of TechnologyTaipeiRepublic of China
  4. 4.Division of Neurosurgery, Department of SurgeryTaitung Br. of Mackay Memorial HospitalTaitungRepublic of China
  5. 5.Department of AnesthesiologyShin Kong Wu Ho-Su Memorial HospitalTaipei CityRepublic of China
  6. 6.Department of NeurosurgeryMackay Memorial HospitalTaipeiRepublic of China
  7. 7.School of MedicineFu Jen Catholic UniversityNew Taipei CityRepublic of China

Personalised recommendations