Abstract
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases and is characterized by progressive dopaminergic neurodegeneration in the substantia nigra pars compacta area. In the present study, treatment of EA for 1 week at a dose of 10 mg/kg body weight prior to MPTP (25 mg/kg body weight) was carried out. MPTP administration caused oxidative stress, as evidenced by decreased activities of superoxide dismutase and catalase, and the depletion of reduced glutathione with a concomitant rise in the lipid peroxidation product, malondialdehyde. It also significantly increased the pro-inflammatory cytokines and elevated the inflammatory mediators like cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the striatum. Immunohistochemical analysis revealed a loss of dopamine neurons in the SNc area and a decrease in dopamine transporter in the striatum following MPTP administration. However, treatment with EA prior to MPTP injection significantly rescued the dopaminergic neurons and dopamine transporter. EA treatment further restored antioxidant enzymes, prevented the depletion of glutathione and inhibited lipid peroxidation, in addition to the attenuation of pro-inflammatory cytokines. EA also reduced the levels of COX-2 and iNOS. The findings of the present study demonstrate that EA protects against MPTP-induced PD and the observed neuroprotective effects can be attributed to its potent antioxidant and anti-inflammatory properties.
Highlights
Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with selective loss of nigrostriatal dopamine (DA) neurons and the presence of intraneuronal cytoplasmic inclusions known as Lewy bodies
MPTP administration caused a significant death of DA neurons in the SNc area and a decrease in density of striatal DA fibers of mice when compared to vehicle-injected control mice
ellagic acid (EA) alone did not cause any harmful effect on DA neurons in SNc and or its nerve terminal in the striatum (Figure 1)
Summary
Parkinson’s disease (PD) is a progressive neurodegenerative disorder associated with selective loss of nigrostriatal dopamine (DA) neurons and the presence of intraneuronal cytoplasmic inclusions known as Lewy bodies. Among the various dopaminergic neurotoxins used to create a PD animal model, MPTP has received much attention due to its capability to produce clinical features of PD in humans and monkeys. It causes the death of dopamine neurons by inhibiting complex I of the mitochondrial electron transport chain and produces Parkinsonism in experimental animals like rodents and primates. It displaces the neurotransmitter, dopamine molecule, from the synaptic vesicle and enhances dopamine autoxidation in the cytosol to generate reactive oxygen species that are detrimental to the neurons. MPTP exposure in mice does not produce LB-like protein aggregates and is not associated with α-syn aggregation
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