2006, Number 3
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Otorrinolaringología 2006; 51 (3)
Intracerebral injection (sustantia nigra compacta) of dextran ferrum as an experimental model of Parkinson’s disease
Alfaro RA, González PR, Padilla MK, Uribe ER
Language: Spanish
References: 27
Page: 105-110
PDF size: 280.12 Kb.
ABSTRACT
Background
Parkinson’s disease (PD) is featured by progressive and selective destruction in the nigrostriatal dopaminergic neurons. Dopamine’s oxidative metabolism, the hydrogen peroxide (H2O2) generation and the production of the 6-hydroxydopamine neurotoxin have been associated. H2O2 may damage directly to the tissues or facilitate the productions of oxygen free radicals. Such a fact is enhanced by low levels of antioxidant enzymes such as glutation peroxidase, superoxido dismutase and catalase, which are found in the central nervous system in some extent.
Objective
To develop a Parkinson’s disease experimental model by means of the study of the neurochemical and behavioral effects after the administration of 1μl of dextran Ferrum (D Fe) into the sustantia nigra compacta (SNc) by means of a micropipette (10 μm thick).
Material and methods
40 male wistar rats were used (260-310 g). D Fe was injected in the right SNc and their motor performance was evaluated during 30 days. Another group was decapitated after either, 7 or 30 days in order to obtain the striatum dopamine content were analyzed by means of high performance liquid chromatography. Results were analyzed by means of an ANOVA and a pos hoc Tukey t test (p ‹ 0.001).
Results
Behavioral test showed that the animals maintained a head’s inclination contralateral to the microinjection’s site, increasing gradually along time post-injection. Moreover, contralateral fore and hindlimb crawling, and contralateral rotational movements were also observed. On the other hand, dopamine levels decreased after 7 and 30 days post-injection.
Conclusion
The D Fe injection accelerated the peroxydation mechanisms, leading to a progressive development of Parkinson's disease.
REFERENCES
Pisa M. Motor somatopy in the striatum of rat: manipulation, biting and gait. Behav Brian Res 1988;27:21-35.
Rinne JO, Rummukainen J, Paijarvi L, Rinne UK. Dementia in Parkinson’s disease is related to neuronal loss in the medial substantia nigra. Ann Neurol 1989;26:47-50.
Harman D. The free radical theory of aging. Antioxid Redox Signal 2003;5(5):557-61.
Zigmond MJ, Strikcker EM. Parkinson’s disease: Studies with an animal model. Life Sci 1984;35:5-18.
Halliwell B, Gutteridge JMC. Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem J 1984;219:1-14.
Evans PH. Free radicals in brain metabolism and pathology. Br Med Bull 1993;49(3):577-87.
Sziráki I, Rauhala P, Chiueh CC. Novel protective effect of manganese against ferrous citrate-induced lipid peroxidation and nigrostriatal neurodegeneration in vivo. Brain 1995;698:285-7.
Thiffault C, Aumont N, Quirion R, Poirier J. Effect of MIPTP and L-Deprenyl on antioxidant enzymes and lipid peroxidation levels in mouse brain. J Neurochem 1995;65(6):2725-33.
Hirsch E, Graybiel AM, Agid YA. Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson’s disease. Nature 1988;334:345-8.
Hirsch EC, Mouatt A, Faucheux B, et al. Dopamine, tremor, and Parkinson’s disease. Lancet 1992;340:25-126.
Sengstock GJ, Olanow CW, Dunn AJ, Arendash GW. Iron induces degeneration of nigrostriatal neurons. Br Res Bull 1992;28:645-9.
Sengstock GJ, Olanow CW, Dunn AJ, Barone S, Arendash GW. Progressive changes in striatal dopaminergic markers, nigral volume, and rotational behavior following iron infusion into the rat substantia nigra experimental. Neurology 1994;130:82-94.
Paxinos G, Watson Ch. The rat brain in stereotaxic coordinates. New York: Academic Press, 1982.
Glowinski J, Iversen LL. Regional studies of catecholamines in the rat brain-I. The disposition of (H3) Norepinephrine, (H3) dopamine and (H3) dopa in various regions of the brain. J Neurochem 1996;3:665-9.
Poirier LJ, Giguere M, Marchand R. Comparative morphology of the substantia nigra and ventral tegmental area in the monkey, cat and rat. Brain Res Bull 1983;11(3):371-97.
Perry TL, Goidin DV, Hasen S. Parkinson’s disease: a disorder due to nigral glutathione deficiency? Neurosci Lett 1982;33:305-10.
Langston JW. Mechanisms underlying neuronal degeneration in Parkinson’s disease: an experimental and theoretical treatise. Mov Dis 1989;4:5-S25.
Muntané J, Puig-Parellada P, Mitjavila MT. Iron metabolism and oxidative stress during acute and chronic phases of experimental inflammation: Effect of iron-dextran and deferoxamine. J Lab Clin Med 1995;126(5):435-43.
Konradi C, Kornhuber J, Froelich L, et al. Demonstration of monoamine oxidase A and B in the human brainstem by a histochemical technique. Neurosci 1989;33:383-400.
Agid Y, Ruberg M, Javoy-Agid F, et al. Are dopaminergic neurons selectively vulnerable to Parkinson’s disease? Adv Neuron 1993;60:148-64.
Ebadi M, Srinivasan SK. Oxidative stress and antioxidant therapy in Parkinson’s disease. Prog Neurobiol 1996;48:1-19.
Thiffault C, Aumont N, Quirion R, Poirier J. Effect of MIPTP and L-Deprenyl on antioxidant enzymes and lipid peroxidation levels in mouse brain. J Neurochem 1995;65(6):2725-33.
Agid Y, Javoy F, Glowinski J. Hyperactivity of remaining dopaminergic neurons after partial destruction of the nigrostriatal dopaminergic system in the rat. Nature 1973;245:150-1.
Anden NE, Roos BE, Weidinius B. Effects of chlorpromazine, haloperidol and reserpine on the levels of phenolic acids in rabbit corpus striatum. Life Sci 1964;3:149-58.
Janssen PAJ, Jagenau AHM, Schellekens KHL. Chemistry and pharmacology of compounds related to 4-(4-hydroxy-4-phenyl-piperidino)- Butyrophenone. Influence of haloperidol (R 1625) and of chlorpromazine en the behavior of rats in an unfamiliar ‘Open field” situation. Psychopharmacol 1960;1:389-92.
Marshall JF, Teitelbaum P. Further analysis of sensory inattention following lateral hypothalamic damage in rats. J Comp Physiol Psychol 1974;86:375-95.
Ungerstedt U. Adipsia and aphagia after 6-hydroxydopamine induced degeneration of the nigrostriatal dopaminergic system in the rat. Acta Physiol Scand 1971;367:95-122.