Brain nigrostriatal system changes in rotenone-induced parkinsonism (quantitative immune-morphological study)

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Abstract

For studying one of the commonest diseases of the nervous system, parkinsonism, long-term course of injections of pesticide rotenone to Wistar rats was used, and thereafter changes of neurons and glial cells in the nigrostriatal regions of the brain were investigated by immunohistochemical methods. It was found that rats treated by rotenone were characterized by reduced motor activity and displayed characteristics of experimental parkinsonism. These changes were accompanied by a decreased tyrosine hydroxylase staining in the processes of the s. nigra dopamine neurons and aggregation of α-synuclein in their bodies, as well as by significant loss of dopamine cells in the rostral part of the s.nigra. Rotenone produced bilateral local destruction of brain tissue with surrounding activated astrocytes in the dorsal parts of the striatum bilaterally. One may conclude that a parkinsonian model induced by rotenone is characterized by degenerative changes of dopamine neurons in the s. nigra, with α-synuclein aggregation and local and symmetrical injury of the striatum (with the involvement of dopaminergic fibers, neurons, neuroglia and cerebral vessels), which presumably reflects rotenone-induced mitochondrial dysfunction.

 
 

About the authors

Dmitriy N. Voronkov

Research Center of Neurology

Author for correspondence.
Email: voronkovdm@gmail.com
Россия, Moscow

Yu. V. Dikalova

Research Center of Neurology

Email: platonova@neurology.ru
Россия, Moscow

Rudolf M. Khudoerkov

Research Center of Neurology

Email: voronkovdm@gmail.com
Россия, Moscow

Nina G. Yamshchikova

Research Center of Neurology

Email: voronkovdm@gmail.com
Россия, Moscow

References

  1. Степанова М.С., Беляев М.С., Стволинский С.Л. Действие карнозина на крыс при гипоксии, отягощенной 3-нитропропионатом. Нейрохимия 2005; 22: 128–132.
  2. Худоерков Р.М., Воронков Д.Н. Количественная оценка нейронов и нейроглии с помощью компьютерной морфометрии. Бюлл. эксперим. биол. мед. 2010; 1: 109–113.
  3. Alam M., Schmidt W.J. l-DOPA reverses the hypokinetic behavior and rigidity in rotenone-treated rats. Behav. Brain Res. 2004; 153: 439–446.
  4. Bancroft J.D., Gamble M. Theory and Practice of Histological Techniques. 5th ed. London: Churchill Livingstone 2002: 303–320.
  5. Betarbet R., Sherer T.B., MacKenzie G. et al. Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat. Neurosci. 2000; 3: 1301–1306.
  6. Cicchetti F., Drouin-Ouellet J., Gross R.E. Environmental toxins and Parkinson’s disease: what have we learned from pesticide-induced animal models? Trends Pharmacol. Sci. 2009; 30: 475–483.
  7. Choi W.-S., Palmiter R.D., Zhengui X. Loss of mitochondrial complex I activity potentiates dopamine neuron death induced by microtubule dysfunction in a Parkinson’s disease model. Cell Biol. 2011; 192: 873–882.
  8. Choi W.-S., Kruse S.E., Palmiter R.D. et al. Mitochondrial complex I inhibition is not required for dopaminergic neuron death induced by rotenone, MPP+, or paraquat. PNAS 2008; 105: 15136–15141.
  9. Dickson D.W. Parkinson’s Disease and Parkinsonism: Neuropathology. Cold Spring Harb. Perspect. Med. 2012; 2 (8): doi: 10.1101/cshperspect.a009258.
  10. Drolet R.E., Cannon J.R., Montero L. et al. Chronic rotenone exposure reproduces Parkinson’s disease gastrointestinal neuropathology. Neurobiol. Dis. 2009; 36: 96–102.
  11. Fritsch T., Smyth K.A., Wallendal M.S. et al. Parkinson Disease: Research Update and Clinical Management. South Med. J. 2012; 105: 650–656.
  12. Gorell J.M., Johnson C.C., Rybicki B.A. et al. The risk of Parkinson’s disease with exposure to pesticides, farming, well water, and rural living. Neurology 1998; 50:1346–1350.
  13. Höglinger G.U., Feger J., Prigent A. et al. Chronic systemic complex I inhibition induces a hypokinetic multisystem degeneration in rats. J. Neurochem. 2003; 84: 491–502.
  14. Lehmensiek V., Tan E.M., Schwarz J. et al. Expression of mutant alpha-synucleins enhances dopamine transporter-mediated MPP+ toxicity in vitro. Neuroreport 2002; 13: 1279–1283.
  15. Liou H.H., Tsai M.C., Chen C.J. et al. Environmental risk factors and Parkinson’s disease: a case-control study in Taiwan. Neurology 1997; 48: 1583–1588.
  16. Massano J., Bhatia K.P. Clinical Approach to Parkinson’s Disease: Features, Diagnosis, and Principles of Management. Cold Spring Harb. Perspect. Med. 2012; 2 (6): doi: 10.1101/cshperspect.a008870.
  17. Panickar K.S., Norenberg M.D. Astrocytes in cerebral ischemic injury: morphological and general considerations. Glia. 2005; 50: 287–298.
  18. Paxinos G., Watson C. The Rat Brain in Stereotaxic Coordinates. Academic Press, 2008.
  19. Radad K., Hassanein K., Moldzio R. et al. Vascular damage mediates neuronal and non-neuronal pathology following short and long-term rotenone administration in Sprague-Dawley rats. Exp. Toxicol. Pathol. 2013; 65: 41–47.
  20. Salvatore M.F., Pruett B.S. Dichotomy of tyrosine hydroxylase and dopamine regulation between somatodendritic and terminal field areas of nigrostriatal and mesoaccumbens pathways. PLoS One 2012; 7: e29867.
  21. Schmued L.C., Stowers C.C., Scallet A.C. et al. Fluoro-Jade C results in ultra high resolution and contrast labeling of degenerating neurons. Brain Res. 2005; 1035: 24–31.
  22. Sherer T.B., Betarbet R., Kimb J.-H. et al. Selective microglial activation in the rat rotenone model of Parkinson’s disease. Neurosci. Lett. 2000; 341: 87–90.
  23. Sherer T.B., Betarbet R., Testa C.M. et al. Mechanism of toxicity in rotenone models of Parkinson’s disease. J. Neurosci. 2003; 23: 10756–10764.
  24. Shigeno T., McCulloch J., Graham D.I. et al. Pure cortical ischemia versus striatal ischemia. Circulatory, metabolic, and neuropathologic consequences. Surg. Neurol 1985; 24: 47–51.
  25. Uversky V.N. Neurotoxicant-induced animal models of Parkinson’s disease: understanding the role of rotenone, maneb and paraquat in neurodegeneration. Cell Tissue Res. 2004; 318: 225–241.
  26. Watabe M., Nakaki T. Mitochondrial complex I inhibitor rotenone inhibits and redistributes vesicular monoamine transporter 2 via nitration in human dopaminergic SH-SY5Y cells. Mol. Pharmacol. 2008; 74: 933–940.
  27. Yang W., Chen L., Ding Y. et al. Paraquat induces dopaminergic dysfunction and proteasome impairment in DJ-1-deficient mice. Hum. Mol. Genet 2007; 16: 2900–2910.
  28. Yoshioka H., Niizuma K., Katsu M. et al. NADPH oxidase mediates striatal neuronal injury after transient global cerebral ischemia. Cerebral Blood Flow Metab. 2011; 31: 868–880.
  29. Zhu C., Vourc’h P., Fernagut P. et al. Variable effects of chronic subcutaneous administration of rotenone on striatal histology. Comp. Neurol. 2004; 478: 418–426.

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Copyright (c) 2013 Voronkov D.N., Dikalova Y.V., Khudoerkov R.M., Yamshchikova N.G.

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