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Портал Begell Электронная Бибилиотека e-Книги Журналы Справочники и Сборники статей Коллекции
Journal of Environmental Pathology, Toxicology and Oncology
Импакт фактор: 1.625 5-летний Импакт фактор: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN Печать: 0731-8898
ISSN Онлайн: 2162-6537

Выпуски:
Том 39, 2020 Том 38, 2019 Том 37, 2018 Том 36, 2017 Том 35, 2016 Том 34, 2015 Том 33, 2014 Том 32, 2013 Том 31, 2012 Том 30, 2011 Том 29, 2010 Том 28, 2009 Том 27, 2008 Том 26, 2007 Том 25, 2006 Том 24, 2005 Том 23, 2004 Том 22, 2003 Том 21, 2002 Том 20, 2001

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.2019030362
pages 1-12

Clozapine Improves Behavioral and Biochemical Outcomes in a MK-801-Induced Mouse Model of Schizophrenia

Syed Suhail Andrabi
Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India
Shruti Vishnoi
Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India
Riya Madan
Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India
Neha Bhardwaj
Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India
Heena Tabassum
Division of Biomedical Sciences, Indian Council of Medical Research, Ministry of Health and Family Welfare, Government of India, V. Ramalingaswamy Bhawan, New Delhi 110029, India
Mohd. Akram
Dept. of Tahaffuzi wa Samaji Tibb, School of Unani Medical Education and Research, Jamia Hamdard, New Delhi 110062, India
Suhel Parvez
Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India

Краткое описание

Glutamatergic N-methyl-D-aspartate (NMDA) receptors have critical roles in several neurological and psychiatric diseases. Dizocilpine (MK-801) is a ligand at phencyclidine recognition sites that is associated with NMDA receptor-coupled cation channels, where it acts as a potent noncompetitive antagonist of central glutamate receptors. In this study, we investigate the effect of clozapine on MK-801-induced neurochemical and neurobehavioral alterations in the prefrontal cortex of mice. Acute administration of NMDA noncompetitive antagonist MK-801 impairs motor coordination, grip strength, and locomotor activity. Clozapine is the only medication that is indicated for treating refractory schizophrenia, due to its superior efficacy among all antipsychotic agents; however, its mechanism is not well understood. To understand its mechanism, we investigated the effects of clozapine on motor coordination, locomotor activity, and grip strength in mice against the NMDA receptor antagonist MK-801. MK-801 induced elevations in acetylcholinesterase (AChE) activity, monoamine oxidase (MAO) activity, and c-fos expression. The administration of clozapine inhibited the effects caused by MK-801 (0.2 mg/kg body weight). Motor coordination and grip strength paradigms that had been altered by MK-801 were restored by clozapine. Moreover, clozapine also ameliorated MK-801-induced elevation in AChE and MAO activity. Our immunostaining results demonstrated that clozapine treatment reduced overexpression of the neuronal activity marker c-fos in cortices of the brain. Results of the current study determine that clozapine ameliorated cognition in MK-801-treated mice via cholinergic and neural mechanisms. These findings show that clozapine possesses the potential to augment cognition in diseases such as schizophrenia.

Ключевые слова: glutamate receptors, schizophrenia, open field, c-fos

ЛИТЕРАТУРА

  1. Forsingdal A, Jorgensen TN, Olsen L, Werge T, Didriksen M, Nielsen J. Can animal models of copy number variants that predispose to schizophrenia elucidate underlying biology? Biol Psychiatry. 2019 Jan 1;85(1):13-24.

  2. Joseph B, Narayanaswamy JC, Venkatasubramanian G. Insight in schizophrenia: relationship to positive, negative and neurocognitive dimensions. Indian J Psych Med. 2015;37(1):5-11.

  3. Barch DM, Ceaser A. Cognition in schizophrenia: core psychological and neural mechanisms. Trends Cogn Sci. 2012;16(1):27-34.

  4. Jirsaraie RJ, Sheffield JM, Barch DM. Neural correlates of global and specific cognitive deficits in schizophrenia. Schizophr Res. 2018 Nov;201:237-42.

  5. Balu DT. The NMDA receptor and schizophrenia: from pathophysiology to treatment. Adv Pharmacol. 2016; 76:351-82.

  6. Winship IR, Dursun SM, Baker GB, Balista PA, Kandratavicius L, Maia-de-Oliveira JP, Hallak J, Howland JG. An overview of animal models related to schizophrenia. Can J Psychiatry. 2019 Jan;64(1):5-17.

  7. Lindsley CW, Shipe WD, Wolkenberg SE, Theberge CR, Williams DL, Jr, Sur C, Kinney GG. Progress towards validating the NMDA receptor hypofunction hypothesis of schizophrenia. Curr Top Med Chem. 2006;6(8):771-85.

  8. Xi D, Zhang W, Wang HX, Stradtman GG, Gao WJ. Dizocilpine (MK-801) induces distinct changes of V-methyl-D-aspartic acid receptor subunits in parvalbumin-containing interneurons in young adult rat prefrontal cortex. Int J Neuropsychopharmacol. 2009 Nov;12(10): 1395-408.

  9. Shiwaku H, Umino A, Umino M, Nishikawa T. Phencyclidine-induced dysregulation of primary cilia in the rodent brain. Brain Res. 2017;1674:62-9.

  10. Reppa I, Williams KE, Worth ER, Greville WJ, Saunders J. Memorable objects are more susceptible to forgetting: evidence for the inhibitory account of retrieval-induced forgetting. Acta Psychol. 2017;181:51-61.

  11. Kovacic P, Somanathan R. Clinical physiology and mechanism of dizocilpine (MK-801): electron transfer, radicals, redox metabolites and bioactivity. Oxidat Med Cell Long. 2010;3(1):13-22.

  12. Rompala GR, Zsiros V, Zhang S, Kolata SM, Nakazawa K. Contribution of NMDA receptor hypofunction in prefrontal and cortical excitatory neurons to schizophrenia-like phenotypes. PLoS One. 2013;8(4):e61278.

  13. Leo RJ, Regno PD. Atypical antipsychotic use in the treatment of psychosis in primary care. Prim Care Comp J Clin Psych. 2000;2(6):194-204.

  14. Vigen CL, Mack WJ, Keefe RS, Sano M, Sultzer DL, Stroup TS, Dagerman KS, Hsiao JK, Lebowitz BD, Lyketsos CG, Tariot PN. Cognitive effects of atypical antipsychotic medications in patients with Alzheimer's disease: outcomes from CATIE-AD. Am J Psych. 2011;168(8): 831-9.

  15. Hill SK, Bishop JR, Palumbo D, Sweeney JA. Effect of second-generation antipsychotics on cognition: current issues and future challenges. Expert Rev Neurother. 2010;10(1):43-57.

  16. Ashafaq M, Raza SS, Khan MM, Ahmad A, Javed H, Ahmad ME, Tabassum R, Islam F, Siddiqui MS, Safhi MM, Islam F. Catechin hydrate ameliorates redox imbalance and limits inflammatory response in focal cerebral ischemia. Neurochem Res. 2012;37(8):1747-60.

  17. Ashafaq M, Khan MM, Shadab Raza S, Ahmad A, Khuwaja G, Javed H, Khan A, Islam F, Siddiqui MS, Safhi MM, Islam F. S-allyl cysteine mitigates oxidative damage and improves neurologic deficit in a rat model of focal cerebral ischemia. Nutr Res. 2012 Feb;32(2):133-43.

  18. Zhou Z, Wang Y, Tan H, Bharti V, Che Y, Wang JF. Chronic treatment with mood stabilizer lithium inhibits amphetamine-induced risk-taking manic-like behaviors. Neurosci Lett. 2015;603:84-8.

  19. Vishnoi S, Raisuddin S, Parvez S. Modulatory effects of an NMDAR partial agonist in MK-801-induced memory impairment. Neuroscience. 2015;311:22-33.

  20. Wickens MM, Bangasser DA, Briand LA. Sex differences in psychiatric disease: a focus on the glutamate system. Front Mol Neurosci. 2018;11:197.

  21. He J, Kong J, Tan QR, Li XM. Neuroprotective effect of atypical antipsychotics in cognitive and non-cognitive be-havioral impairment in animal models. Cell Adhes Migr. 2009;3(1):129-37.

  22. Field JR, Walker AG, Conn PJ. Targeting glutamate synapses in schizophrenia. Trends Mol Med. 2011;17(12): 689-98.

  23. Nestler EJ, Hyman SE. Animal models of neuropsychiatry disorders. Nat Neurosci. 2010;13(10):1161-9.

  24. Poulsen MH, Andersen J, Christensen R, Hansen KB, Traynelis SF, Stromgaard K, Kristensen AS. Binding of ArgTX-636 in the NMDA receptor ion channel. J Mol Biol. 2015;427(1):176-89.

  25. Guo H, Camargo LM, Yeboah F, Digan ME, Niu H, Pan Y, Reiling S, Soler-Llavina G, Weihofen WA, Wang HR, Shanker YG. A NMDA-receptor calcium influx assay sensitive to stimulation by glutamate and glycine/D-serine. Sci Rep. 2017;7(1):11608.

  26. van der Staay FJ, Rutten K, Erb C, Blokland A. Effects of the cognition impairer MK-801 on learning and memory in mice and rats. Beh Brain Res. 2011;220(1):215-29.

  27. Moy SS, Nonneman RJ, Shafer GO, Nikolova VD, Riddick NV, Agster KL, Baker LK, Knapp DJ. Disruption of social approach by MK-801, amphetamine, and fluoxetine in adolescent C57BL/6J mice. Neurotoxicol Teratol. 2013;36:36-46.

  28. Ravan M, Hasey G, Reilly JP, MacCrimmon D, Khodayari-Rostamabad A. A machine learning approach using auditory odd-ball responses to investigate the effect of clozapine therapy. Clin Neurophysiol. 2015;126(4):721-30.

  29. Krishna R, Ali M, Moustafa AA. Effects of combined MAO-B inhibitors and levodopa vs. monotherapy in Parkinson's disease. Front Aging Neurosci. 2014;6:180.

  30. Wong P, Sze Y, Gray LJ, Chang CC, Cai S, Zhang X. Early life environmental and pharmacological stressors result in persistent dysregulations of the serotonergic system. Front Beh Neurosci. 2015;9:94.

  31. Barbelivien A, Nyman L, Haapalinna A, Sirvio J. Inhibition of MAO-A activity enhances behavioural activity of rats assessed using water maze and open arena tasks. Pharmacol Toxicol. 2001;88(6):304-12.

  32. Greenshaw AJ, Turrkish S, Davis BA. The enigma of conditioned taste aversion learning: Stimulus properties of 2-phenylethylamine derivatives. Physiol Res. 2002;51(Suppl 1):S13-20.

  33. Kang H, Park P, Bortolotto ZA, Brandt SD, Colestock T, Wallach J, Collingridge GL, Lodge D. Ephenidine: a new psychoactive agent with ketamine-like NMDA receptor antagonist properties. Neuropharmacology. 2017;112(Pt A):144-9.

  34. Mohammad D, Chan P, Bradley J, Lanctot K, Herrmann N. Acetylcholinesterase inhibitors for treating dementia symptoms-A safety evaluation. Exp Op Drug Safety. 2017;16(9):1009-19.

  35. Csernansky JG, Martin M, Shah R, Bertchume A, Colvin J, Dong H. Cholinesterase inhibitors ameliorate behavioral deficits induced by MK-801 in mice. Neuropsychopharmacology. 2005;30(12):2135-43.

  36. Obermayer J, Verhoog MB, Luchicchi A, Mansvelder HD. Cholinergic modulation of cortical microcircuits is layer-specific: evidence from rodent, monkey and human brain. Front Neural Circuits. 2017;11:100.

  37. Suhail M. Na, K-ATPase: Ubiquitous multifunctional transmembrane protein and its relevance to various patho-physiological conditions. J Clin Med Res. 2010;2(1):1-17.

  38. de Lores Arnaiz GR, Ordieres MG. Brain Na+, K+-AT- Pase activity in aging and disease. Int J Biomed Sci. 2014;10(2):85-102.

  39. Barygin OI, Nagaeva EI, Tikhonov DB, Belinskaya DA, Vanchakova NP, Shestakova NN. Inhibition of the NMDA and AMPA receptor channels by antidepressants and antipsychotics. Brain Res. 2017;1660:58-66.

  40. Bahrami S, Drablos F. Gene regulation in the immediate-early response process. Adv Bio Reg. 2016;62:37-49.

  41. Qiu ZY, Ding Y, Cui LY, Hu ML, Ding MX. The expression patterns of c-Fos and c-Jun induced by different frequencies of electroacupuncture in the brain. Evidence-Based Compl Alt Med. 2015. doi:10.1155/2015/343682.

  42. Nowak K, Meyza K, Nikolaev E, Hunt MJ, Kasicki S. Local blockade of NMDA receptors in the rat prefrontal cortex increases c-Fos expression in multiple subcortical regions. Acta Neurobiol Exp. 2012;72(3):207-18.

  43. Dawson N, Morris BJ, Pratt JA. Subanaesthetic ketamine treatment alters prefrontal cortex connectivity with thalamus and ascending subcortical systems. Schizophr Bull. 2013;39(2):366-77.

  44. Rame M, Caudal D, Schenker E, Svenningsson P, Spedding M, Jay TM, Godsil BP. Clozapine counteracts a ketamine-induced depression of hippocampal-prefrontal neuroplasticity and alters signaling pathway phosphorylation. PLoS One. 2017;12(5):e0177036.

  45. Miller R. Mechanisms of action of antipsychotic drugs of different classes, refractoriness to therapeutic effects of classical neuroleptics, and individual variation in sensitivity to their actions: Part II. Curr Neuropharmacol. 2009;7(4):315-30.

  46. Kuroda K, Suzumura K, Shirakawa T, Hiraishi T, Nakahara Y, Fushiki H, Honda S, Naraoka H, Miyoshi S, Aoki Y. Investigation of mechanisms for MK-801-induced neurotoxicity utilizing metabolomic approach. Toxicol Sci. 2015;146(2):344-53.

  47. Ueno H, Suemitsu S, Murakami S, Kitamura N, Wani K, Takahashi Y, Matsumoto Y, Okamoto M, Ishihara T. Behavioural effects of inhalation exposure to dizocilpine (MK-801) in mice. Biomed Pharmacother. 2019 Jun 6;117:109038. doi: 10.1016/j.biopha.2019.109038.


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