MPTP-induced parkinsonism in mice alters striatal and nigral xCT expression but is unaffected by the genetic loss of xCT
| Autor: | Charles K. Meshul, Madeline J Churchill, Eduard-Mihai Bentea, Ann Massie, Hideyo Sato, Joeri Van Liefferinge, Michelle D Sconce |
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| Přispěvatelé: | Pharmaceutical and Pharmacological Sciences, Experimental Pharmacology, Neuro-Aging & Viro-Immunotherapy |
| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Amino Acid Transport System y+ Tyrosine 3-Monooxygenase Dopamine animal diseases Excitotoxicity Substantia nigra Striatum medicine.disease_cause chemistry.chemical_compound Parkinsonian Disorders Internal medicine Forelimb medicine Animals Mice Knockout Neurons Tyrosine hydroxylase General Neuroscience MPTP Neurodegeneration Dopaminergic Glutamate receptor medicine.disease Corpus Striatum nervous system diseases Substantia Nigra Endocrinology nervous system chemistry 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine 3 4-Dihydroxyphenylacetic Acid Neuroscience |
| Zdroj: | Neuroscience Letters. 593:1-6 |
| ISSN: | 0304-3940 |
| Popis: | Nigral cell loss in Parkinson’s disease (PD) is associated with disturbed glutathione (GSH) and glutamate levels, leading to oxidative stress and excitotoxicity, respectively. System xc- is a plasma membrane antiporter that couples cystine import (amino acid that can be further used for the synthesis of GSH) with glutamate export to the extracellular environment, and can thus affect both oxidative stress and glutamate excitotoxicity. In the current study, we evaluated the involvement of system xc- in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Our results indicate that the expression of xCT (the specific subunit of system xc-) undergoes region-specific changes in MPTP-treated mice, with increased expression in the striatum, and decreased expression in the substantia nigra. Furthermore, mice lacking xCT were equally sensitive to the neurotoxic effects of MPTP compared to wild-type (WT) mice, as they demonstrate similar decreases in striatal dopamine content, striatal tyrosine hydroxylase (TH) expression, nigral TH immunopositive neurons and forelimb grip strength, five weeks after commencing MPTP treatment. Altogether, our data indicate that progressive lesioning with MPTP induces striatal and nigral dysregulation of system xc-. However, loss of system xc- does not affect MPTP-induced nigral dopaminergic neurodegeneration and motor impairment in mice. |
| Databáze: | OpenAIRE |
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