Neuropathological changes induced by neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in male Swiss albino mice

Abstract

We investigated the level of dopamine in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated male Swiss albino mice (40 mg/kg), after 7 days, we measured the levels of non-enzymatic antioxidants, the reduced glutothione (GSH), enzymatic anti-oxidants such as superoxide dismulase (SOD), cataloes (CAT) and also observed the histopathology of the mesencephalic areas after MPTP treatment by transmission electron microscopy (EM). We found that the MPTP treatment in mice caused a significant depletion of GSH, increased the specific activity of SOD, CAT, and thiobarbituric acid–reactive substances (TBARS) in mesencephalic region after 7 days of treatment, and decreased the striatal dopamine level to 75% by 7 days of MPTP treatment. The EM results also suggested that the mitochondrial alternation, nuclear membrane invagination, condensation of cytoplasm, vacuoles and perinuclear inclusion in the cytoplasm, and nuclear membrane disappearance were observed in MPTP-treated mice.

Keywords

cat dopamine GSH MPTP SOD ultra structure

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References

Baba M Takeshige K Bala N Ohsumi Y (1994) Ultrastrutural analysis of the autophagic process in yeast : deliction of autophagosome and this characterization. J Cell Biol 124: 903–913.

Baum RM; (1985) New variety of street drugs poses growing prolong. Chem Eng 7: 7–16.

Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82: 70–77.

Hallman H; Lange J; Olson L; Stromberg I; Jonsson G; (1985) Neurochemical and histochemical charcterisation of neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on brain calicholamine. J Neurochem 44: 117–127.

Heikkila RE Hess A Duvoisin RC (1984) Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. Science 224: 1451–1453.

Irwin I Langston JW (1985) Selective accumulation of MPP+ in the Substantia nigra : a key to Neurotoxicity. Life Sci 36: 207–212.

Kakkar P Das B Viswanathan PN (1984) A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 21: 130–132.

Langston JW (1985a) MPTP and Parkinson’s disease. Trends Neurosci 8: 79–83.

Langston JW (1985b) MPTO neurotoxicity: an overview and characterization of phases of toxicity. Life Sci 36: 201–206.

10.

Lowry OH Rosebrough NJ Farr AL Randall RJ (1954) Protein measurement with Folin phenol reagent. J Biol Chem 193: 265–275.

11.

Nichans WG Samuelson D (1968) Formation of malonaldehyde from pospholipid arrachidonate during microsomal lipid peroxidation. Eur J Biochem 6: 126–130.

12.

Poirier J Barbeau A (1985) A catalyst function for MPTP in superoxide formation. Biochem Biophys Res Commun 131: 1284–1289.

13.

Poirier J Dea D Baccichet A Thiffault C (1994) Superoxide dismutase expression in Parkinson’s diseases. Ann N Y Acad Sci 738: 116–120.

14.

Ramsay RR Kruger MJ Youngster SK Gluck MR Casida JE Singer TP (1991) Interaction of n methyl-4 phenyl pyridinium ion (MMP+) and its analogs with the eotenone/piericidin binding site of NADH dehydro genase. J Neurochem 56: 1184–1190.

15.

Sian J Dexli DT Less AJ (1994) Alliations in glutathione levels in Parkinson’s disease and other neurodegenate discovers affecting basal ganglia. Ann New 36: 348–355.

16.

Singer TP Ramsay RR McKeown K Trevor A Castagnoli A (1988) Mechanism of neurotoxicity of 1-methyl-4-phenylpyridinium (MPP+), the toxic bioactivation product of 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Toxicology 49: 17–23.

17.

Sinha KA (1972) Colorimetric assay of catalase. Anal Biochem 47: 389–394.

18.

Song DD Shults CW Sisk A Rockensteim E Masliach E (2004) Enhanced substantia nigra mitochondrial pathology in human alpha-synuckin transgenic mice after treatment with MPTP. Exp Neurol 186: 158–172.

19.

Tanji H Araki T Nagasawa H Itoyama Y (1999) Differential vulnerability of dopamine receptors in the mouse brain treated with MPTP. Brain Res 824: 224–231.