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CC BY-NC-ND 4.0 · Sleep Sci 2019; 12(03): 196-202
DOI: 10.5935/1984-0063.20190078
ORIGINAL ARTICLE

Absence of a synergic nigral proapoptotic effect triggered by REM sleep deprivation in the rotenone model of Parkinson´s disease

Authors

  • Luana C Kmita

    1   Federal University of Paraná. Department of Physiology - Curitiba - Paraná - Brazil.

  • Jessica L Ilkiw

    1   Federal University of Paraná. Department of Physiology - Curitiba - Paraná - Brazil.

  • Lais S Rodrigues

    1   Federal University of Paraná. Department of Physiology - Curitiba - Paraná - Brazil.
    2   Federal University of Paraná, Department of Pharmacology - Curitiba - Paraná - Brazil.

  • Adriano DS Targa

    1   Federal University of Paraná. Department of Physiology - Curitiba - Paraná - Brazil.
    2   Federal University of Paraná, Department of Pharmacology - Curitiba - Paraná - Brazil.

  • Ana Carolina D Noseda

    1   Federal University of Paraná. Department of Physiology - Curitiba - Paraná - Brazil.
    2   Federal University of Paraná, Department of Pharmacology - Curitiba - Paraná - Brazil.

  • Patrícia dos-Santos

    1   Federal University of Paraná. Department of Physiology - Curitiba - Paraná - Brazil.

  • Juliane Fagotti

    1   Federal University of Paraná. Department of Physiology - Curitiba - Paraná - Brazil.

  • Edvaldo S. Trindade

    3   Federal University of Paraná, Department of Cell Biology - Curitiba - Paraná - Brazil.

  • Marcelo MS Lima

    1   Federal University of Paraná. Department of Physiology - Curitiba - Paraná - Brazil.
    2   Federal University of Paraná, Department of Pharmacology - Curitiba - Paraná - Brazil.
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Excitotoxicity has been related to play a crucial role in Parkinson's disease (PD) pathogenesis. Pedunculopontine tegmental nucleus (PPT) represents one of the major sources of glutamatergic afferences to nigrostriatal pathway and putative reciprocal connectivity between these structures may exert a potential influence on rapid eye movement (REM) sleep control. Also, PPT could be overactive in PD, it seems that dopaminergic neurons are under abnormally high levels of glutamate and consequently might be more vulnerable to neurodegeneration. We decided to investigate the neuroprotective effect of riluzole administration, a N-methyl-D-aspartate (NMDA) receptor antagonist, in rats submitted simultaneously to nigrostrial rotenone and 24h of REM sleep deprivation (REMSD). Our findings showed that blocking NMDA glutamatergic receptors in the SNpc, after REMSD challenge, protected the dopaminergic neurons from rotenone lesion. Concerning rotenone-induced hypolocomotion, riluzole reversed this impairment in the control groups. Also, REMSD prevented the occurrence of rotenone-induced motor impairment as a result of dopaminergic supersensitivity. In addition, higher Fluoro Jade C (FJC) staining within the SNpc was associated with decreased cognitive performance observed in rotenone groups. Such effect was counteracted by riluzole suggesting the occurrence of an antiapoptotic effect. Moreover, riluzole did not rescue cognitive impairment impinged by rotenone, REMSD or their combination. These data indicated that reductions of excitotoxicity, by riluzole, partially protected dopamine neurons from neuronal death and appeared to be effective in relieve specific rotenone-induce motor disabilities.

Excitotoxicity - Neuroprotection - Riluzole - REM sleep deprivation - Intranigral rotenone - Parkinson's disease


Publication History

Received: 02 April 2019

Accepted: 20 August 2019

Article published online:
31 October 2023

© 2023. Brazilian Sleep Association. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • REFERENCES

  • 1 Alam, M, A Mayerhofer and WJ Schmidt (2004). The neurobehavioral chances induced by bilateral rotenone lesion in medial forebrain bundle of rats are reversed by L-DOPA. Bahavioural Brain Research 151: 117-124.
  • 2 Ambrosi, G, S Cerri and F Blandini (2014). A further update on the role of excitotoxicity in the pathogenesis of Parkinson’s disease. Journal of Neurotransmission 121:849-859.
  • 3 Araki, T, Y Muramatsu, K Tanaka, M Matsubara and Y Imai (2001a). Riluzole (2-amino-6-trifluoromethoxy benzothiazole) attenuates MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity in mice. Neuroscience Letters 312:50-54.
  • 4 Araki, T, T Kumagai, K Tanaka, M Matsubara, H Kato, Y Itoyama et al (2001b). Neuroprotective effect of riluzole in MPTP-treated mice. Brain Research 918:176-181.
  • 5 Barnéoud, P, M Mazadier, JM Miquet, S Parmentier, P Dubádat, A Doble. et al (1996). Neuroprotective effects of riluzole on a model of Parkinson’s disease in the rat. Neuroscience 4:971-983.
  • 6 Barraud, Q, V Lambrecq, C Forni, S Mcguire, M Hill, B Bioulac. et al (2009). Sleep disorders in Parkinson’s disease: the contribution of the MPTP non-human primate model. Exp Neurol 219:574-582.
  • 7 Benazzouz, A, T Boraud, P Dubédat, A Boireau, JM Stutzmann, C Gross (1995). Riluzole prevents MPTP-induced parkinsonism in the resus monkey: a pilot study. European Journal of Pharmacology 284:299-307.
  • 8 Biswas, S, P Mishra and BN Mallick (2006). Increased apoptosis in rats brain after rapid eye movement sleep loss. Neuroscience 142:315-331.
  • 9 Boireau, A, P Dubédat, F Bordier, C Peny, JM Miquet, G Durand, et al (1994). Riluzole and experimental parkinsonism: antagonism of MPTPinduced decrease in central dopamine levels in mice. Neuroreport 18:2657-2660.
  • 10 Breit, S, R Bouali-Benazzouz, AL Benabid, A Benazzouz (2001). Unilateral lesion of the nigrostriatal pathway induces an increase of neuronal activity of the pedunculopontine nucleus, wich is reversed by the lesion of the subthalamic nucleus in rats. European Journal of Neuroscience 14:1833-1842.
  • 11 Carbone, M, S Duty and M Rattray (2012). Riluzole neuroprotection in a parkinson’s disease model involves suppression of reactive astrocytosis but not GLT-1 regulation. BMC Neuroscience 13:1-8.
  • 12 Chen, L, S Tian and J Ke (2014). Rapid eye movement sleep deprivation disrupts consolidation but not reconsolidation of novel object recognition memory in rats. Neurosci Lett 20:12-16.
  • 13 Charrara, A, Y Smith and A Parent (1996). Glutamatergic inputs from the pedunculopontine nucleus to midbrain dopaminergic neurons in primates: Phaseolus vulgaris-leucoagglutinin anterograde labeling combined with postembedding glutamate and GABA immunohistochemistry. The journal of Comparative Neurology 364:254-266.
  • 14 Dawson, TM and VL Dawson (2002). Neuroprotective and neurorestorative strategies for Parkinson’s disease. Nature Neuroscience supplement 5:1058-1061.
  • 15 Dere E, MA Silva and JP Huston (2004). Higher order memories for objects encountered in different spatio-temporal contexts in mice: evidence for episodic memory. Rev Neurosci 15:231–240.
  • 16 Doble, A (1999). The role of excitotoxicity in neurodegenerative disease: Implications for therapy. Pharmacol. Ther 81:163-221.
  • 17 Dos Santos, ACD, MAV Castro, EAK Jose, AM Delattre, PA Dombrowski, C Da Cunha. et al (2013). REM sleep deprivation generates cognitive and neurochemical disruptions in the intranigral rotenone model of Parkinson’s disease. Journal of Neuroscience Research 91: 1508-1516.
  • 18 Ennaceur, A and J Delacour (1988). A new one-trial test for neurobiological studies of memory in rats. 1: behavioral data. Behav. Brain Res 31:47-59.
  • 19 Erro, R, G Santangelo, M Picillo, C Vitale, M Amboni, K Longo et al (2012). Link between non-motor symptoms and cognitive dysfunctions in de novo, drug-naïve patients. J Neurol 259:1808-1813.
  • 20 Fagotti J, Targa ADS, Rodrigues, LS, Noseda, ACD, Dorieux, FWC, Scarante, FF, Ilkiw, JL, Louzada, FM, Chowdhury, NR, Van der Veen, DR, Middleton, B, Pennings, J LA, Swann, JR, Skene, DJ, Lima, MMS (2019). Chronic sleep restriction in the rotenone Parkinson’s disease model in rats reveals peripheral early-phase biomarkers. Sci. Reports 9: 1898.
  • 21 Fumagalli, E, M Funicello, T Rauen, M Gobbi, T Mennini (2008). Riluzole enhances the activity of glutamate transporters GLAST, GLT1 and EAAC1. European Journal of Pharmacology 578:171-176.
  • 22 Khadrawy, YA, NA Nour and HSA Ezz (2011). Effect of oxidative stress induced by paradoxal sleep deprivation on the activities of Na+, K+-ATPase and acetylcholinesterase in the cortex and hippocampus of rat. Translational Research 157:100-107.
  • 23 Jaiswal, MK (2017). Riluzole but not melatonin ameliorates acute motor neuron degeneration and moderately inhibits SOD1-mediated excitotoxicity induced disrupted mitochondrial Ca2+ sinaling in amyotrophic lateral sclerosis. Front. Cell. Neurosci 10:1-14.
  • 24 Lang, AE and AM Lozano (1998). Parkinson’s disease. The New England Jounal of Medicine 339:1044-1053.
  • 25 Lavoie, B and A Parent (1994). Pedunculopontine nucleus in the squirrel monkey: Projections to the basal ganglia as revealed by anterograde tracttracing methods. The Journal of Comparative Neurology 344:210-231.
  • 26 Lima, MMS, ML Andersen, AB Reksidler, MABF Vital, S Tufik (2007). The role of the substantia nigra pars compacta in regulating of sleep patterns in rats. PLOS ONE 6:1-7.
  • 27 Lima, MMS, AB Reksidler and MABF Vital (2008). The dopaminergic dilema: Sleep or wake? Implications in Parkinson’s disease. Bioscience Hypotheses 1:9-13.
  • 28 Lima, MMS, ML Andersen, AB Reksidler, AC Ferraz, MABF Vital, S Tufik, S (2012). Paradoxical sleep deprivation modulates tyrosine hydroxylase expression in the nigroestriatal pathway and attenues motor deficits induced by dopaminergic depletion. CNS & Neurological Disorders . Drug Targets 11:359-368.
  • 29 Lima, MMS (2013). Sleep disturbances in Parkinson’s disease: The contribution of dopamine in REM sleep regulation. Sleep Medicine Reviews 17:367-375.
  • 30 Luquin, MR, L Saldise, J Guillen, S Belzunegui, W San Sebastian, A Izal, et al (2006). Does increase excitatory drive from the subthalamic nucleus contribute to dopaminergic neuronal death in Parkinson’s disease? Experimental Neurology 201:407-415.
  • 31 Mena-Segovia, J, JP Bolam and PJ Magill (2004). Pedunculopontine nucleous and basal ganglia: distant relatives or part of the same Family? TRENDS in Neuroscience 27:585-588.
  • 32 Mokhtari, Z, T Baluchnejadmojarad, F Nikbakht, M Mansouri, M Roghani (2017). Riluzole ameliorates learning and memory deficits in Aβ25-35-induced rat model of Alzheimer’s disease and is independent of cholinoceptor activation. Biomedice & Pharmacotherapy 87:135-144.
  • 33 Moreira, CG, D Ariza, PA Dombrowski, P Sabioni, M Bortolanza, C da Cunha, et al (2012). Behavioral, neurochemical and histological alterations promoted by bilateral intranigral rotenone administration. Neurotox Res 21: 291-301.
  • 34 Morris RG (2001). Episodic-like memory in animals: psychological criteria, neural mechanisms and the value of episodic-like tasks to investigate animal models of neurodegenerative disease. Philos Trans R Soc Lond B Biol Sci 356:1453.1465.
  • 35 Munhall, AC, YN Wu, JK Belknap, CK Meshul, SW Johnson (2012). NMDA alters rotenone toxicity in rat substantia nigra zona compacta and ventral tegmental area dopamine neurons. NeuroToxicology 33:429-435.
  • 36 Nunes, GP, S Tufik and JN Nobrega (1994). Autoradiographic analysis of D1 and D2 dopaminergic receptors in rat brain after paradoxical sleep deprivation. Brain Res. Bull 34:453-456.
  • 37 Olney, JW (1969). Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science 164:719-721.
  • 38 Olney, JW (1989). Excitatory amino acids and neuropsychiatric disorders. Biol Psychiatry 26:505-525.
  • 39 Palchykova S, R Winsky-Sommerer, P Meerlo, R Du’Nrr, I Tobler (2006). Sleep deprivation impairs object recognition in mice. Neurobiol Learn Mem 85: 263.271.
  • 40 Paxinos, G and C Watson (2005). The Rat Brain in Stereotaxic Coordinates. 5th edition San Diego: Academic Press.
  • 41 Pierantozzi, M, F Placidi, C Liquori, M Albanese, P Imbriani, MG Marciani, et al. (2016). Ritigotine may improve sleep architecture in Parkinson’s disease: A double-blind, randomized, placebo-controlled polysomnographic study. Sleep Med 21:140-144.
  • 42 Proenca, MB, PA Dombrowski, C Cunha, L Fischer, AC Ferraz and MMS Lima (2014). Dopaminergic D2 receptor is a key player in the substantia nigra par compacta neuronal activation mediated by REM sleep deprivation. Neuropharmacology 76:118-126.
  • 43 Rodrigues, LS, ADS Targa, ACD Noseda, MF Aurich, LC Cunha and MMS Lima (2014). Olfactory impairment in the rotenone model of Parkinson’s disease is associated with bulbar dopaminergic D2 activity after REM sleep deprivation. Frontiers in Cellular Neuroscience 8:1-11.
  • 44 Souchay C, M Isingrini and R Gil (2006). Metamemory monitoring and Parkinson’s disease. J Clin Exp Neuropsychol 28:618.630.
  • 45 Souza, L, SS Smaili, RP Ureshino, R Sinigaglia-Coimbra, ML Andersen, GS Lopes, et al (2012). Effect of chronic sleep restriction and aging on calcium signaling and apoptosis in the hippocampus of young and aged animals. Progress in Neuro-Psychopharmacology & Biological Psychiatry 39:23-30.
  • 46 Sugiyama, A, A Saitoh, M Inagaki, O Jun-Ichiro, M Yamada (2015). Systemic adiministration of riluzole enhances recognition memory and facilitates extinction of fear memory in rats. Neuropharmacology 97:322-328.
  • 47 Schmued, LC, CC Stowers, AC Scallet, L Xu (2005). Fluoro-Jade C results in ultra high resolution and contrast labeling of degenerating neurons. Brain Research 1: 24-34.
  • 48 Targa, ADS, LS Rodrigues, ACD Noseda, M Aurich, ML Andersen, S Tufik, et al. (2016) Unraveling a new circuitry for sleep regulation in Parkinson’s disease. Neuropharmacology 108:161-171.
  • 49 Targa, ADS, ACD Noseda, LS Rodrigues, M Aurich, Lima MMS (2018). REM sleep deprivation and dopaminergic D2 receptors modulation increase recognition memory in an animal model of Parkinson’Ls disease Behav Brain Res 339:239-248.
  • 50 Testa, CM, TB Sherer and JT Greenamyre (2005). Rotenone induces oxidative stress and dopaminergic neuron damage in organotypic substantia nigra cultures. Molecular Brain Research 134:109-118.
  • 51 Tufik S, CJ Lindsey and EA Carlini (1978). Does REM sleep deprivation induce a supersensitivity of dopaminergic receptors in the rat brain? Pharmacology 16:98-105.
  • 52 Tufik S (1981a). Changes of response to dopaminergic drugs in rats submitted to REM-sleep deprivation. Psychopharmacology 72:257.260.
  • 53 Tufik, S (1981b). Increased responsiveness to apomorphine after REM sleep deprivation: supersensitivity of dopamine receptors or increase in dopamine turnover? J. Pharm. Pharmacol 33: 732.
  • 54 Verhave, PS, MJ Jongsma, RM Van Der Berg, RAP Vanwersch, AB Smit, HCHM Philippens (2012). Neuroprotective effects of riluzole in early phase Parkinson’s disease on clinically relevant parameters in the marmoset MPTP model. Neuropharmacology 62:1700-1707.
  • 55 Wu, YN and SW Johnson (2007). Rotenone potentiates NMDA currents in substantia nigra dopamine neurons. Neuroscience Letters 421:96-100.
  • 56 Wu, YN and SW Johnson (2011). Dopamine oxidation facilitates rotenone-dependent potentiation of N-methyl-D-aspartate currents in rat substantia nigra dopamine neurons. Neuroscience 195:138-144.
  • 57 Zhang, ZN, JS Zhang, J Xiang, ZH Yu, W Zhang, M Cai, et al (2017). Subcutaneous rotenone rat model of Parkinson’s disease: Dose exploration study. Brain Research 1655:104-113.
  • 58 Zhang, LY, WY Liu, WY Kang, Q Yang, XY Wang, JQ Ding, et al (2016). Association of rapid eye movement sleep behavior disorder with sleepdisordered breathing in Parkinson’s disease. Sleep Med 20:110-115.