ascorbic-acid and Parkinson-Disease--Secondary

Parkinson's disease (PD) is a neurodegenerative disease characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra (SN). Oxidative stress has been identified as one of the major causes of nigrostriatal degeneration in PD. Ascorbic acid plays a role as an efficient antioxidant to protect cells from free radical damage, but it is easily oxidized and loses its antioxidant activity. To overcome this limitation, we have recently developed NXP031, a single-stranded DNA aptamer that binds to ascorbic acid with excellent specificity, reducing its oxidation and increasing its efficacy. This study investigated the neuroprotective effects of NXP031 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model. Acute degeneration of nigral dopaminergic neurons was induced by four consecutive treatments of MPTP (20 mg/kg) in male C57BL/6 J mice. NXP031 (Vitamin C/Aptamin C 200 mg/4 mg/kg) was administered intraperitoneally for 5 days following MPTP. We observed that the administration of NXP031 ameliorated MPTP-induced loss of dopaminergic neurons in the SN and exhibited improvement of MPTP-mediated motor impairment. We further found that NXP031 increased plasma ascorbic acid levels and inhibited microglia activation-induced neuroinflammation in the SN, which might contribute to the protective effects of NXP031 on nigrostriatal degeneration. Our findings suggest that NXP031 could be a potential therapeutic intervention in PD.

Topics: Animals; Ascorbic Acid; Dopaminergic Neurons; Male; Mice; Mice, Inbred C57BL; Microglia; MPTP Poisoning; Nerve Degeneration; Neuroprotective Agents; Parkinson Disease, Secondary; Postural Balance; Psychomotor Performance; Substantia Nigra

Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the nigrostriatal system and dopamine (DA) depletion in the striatum. The most popular therapeutic medicine for treating PD, 3-(3,4-Dihydroxyphenyl)-L-alanine (L-DOPA), has adverse effects, such as dyskinesia and disease acceleration. As superoxide (·O(2)(-)) and hydroxyl radical (·OH) have been implicated in the pathogenesis of PD, free radical scavenging and antioxidants have attracted attention as agents to prevent disease progression. Rodents injected with 6-hydroxydopamine (6-OHDA) intracerebroventricularly are considered to be a good animal model of PD. Zingerone and eugenol, essential oils extracted from ginger and cloves, are known to have free radical scavenging and antioxidant effects. Therefore, we examined the effects of zingerone and eugenol on the behavioral problems in mouse model and on the DA concentration and antioxidant activities in the striatum after 6-OHDA administration and L-DOPA treatment. Daily oral administration of eugenol/zingerone and injection of L-DOPA intraperitoneally for 4 weeks following a single 6-OHDA injection did not improve abnormal behaviors induced by L-DOPA treatment. 6-OHDA reduced the DA level in the striatum; surprisingly, zingerone and eugenol enhanced the reduction of striatal DA and its metabolites. Zingerone decreased catalase activity, and increased glutathione peroxidase activity and the oxidized L-ascorbate level in the striatum. We previously reported that pre-treatment with zingerone or eugenol prevents 6-OHDA-induced DA depression by preventing lipid peroxidation. However, the present study shows that post-treatment with these substances enhanced the DA decrease. These substances had adverse effects dependent on the time of administration relative to model PD onset. These results suggest that we should be wary of ingesting these spice elements after the onset of PD symptoms.

Topics: Animals; Antioxidants; Ascorbic Acid; Catalase; Corpus Striatum; Disease Models, Animal; Dopamine; Eugenol; Free Radical Scavengers; Glutathione; Glutathione Peroxidase; Guaiacol; Levodopa; Male; Mice; Oxidopamine; Parkinson Disease; Parkinson Disease, Secondary; Superoxide Dismutase

Recent studies demonstrate that rehabilitation ameliorates physical and cognitive impairments of patients with stroke, spinal cord injury, and other neurological diseases and that rehabilitation also has potencies to modulate brain plasticity. Here we examined the effects of compulsive exercise on Parkinson's disease model of rats. Before 6-hydroxydopamine (6-OHDA, 20 microg) lesion into the right striatum of female SD rats, bromodeoxyuridine (BrdU) was injected to label the proliferating cells. Subsequently, at 24 h after the lesion, the rats were forced to run on the treadmill (5 days/week, 30 min/day, 11 m/min). As behavioral evaluations, cylinder test was performed at 1, 2, 3, and 4 weeks and amphetamine-induced rotational test was performed at 2 and 4 weeks with consequent euthanasia for immunohistochemical investigations. The exercise group showed better behavioral recovery in cylinder test and significant decrease in the number of amphetamine-induced rotations, compared to the non-exercise group. Correspondingly, significant preservation of tyrosine hydroxylase (TH)-positive fibers in the striatum and TH-positive neurons in the substantia nigra pars compacta (SNc) was demonstrated, compared to the non-exercise group. Additionally, the number of migrated BrdU- and Doublecortin-positive cells toward the lesioned striatum was increased in the exercise group. Furthermore, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor increased in the striatum by exercise. The results suggest that exercise exerts neuroprotective effects or enhances the neuronal differentiation in Parkinson's disease model of rats with subsequent improvement in deteriorated motor function.

Topics: Amphetamine; Animals; Ascorbic Acid; Behavior, Animal; Brain-Derived Neurotrophic Factor; Bromodeoxyuridine; Cell Proliferation; Corpus Striatum; Disease Models, Animal; Doublecortin Domain Proteins; Doublecortin Protein; Exercise Test; Female; Glial Cell Line-Derived Neurotrophic Factors; Microtubule-Associated Proteins; Movement; Neuropeptides; Oxidopamine; Parkinson Disease, Secondary; Physical Conditioning, Animal; Rats; Rats, Sprague-Dawley; Rotation; Substantia Nigra; Time Factors; Tyrosine 3-Monooxygenase

To investigate whether high dietary intake of antioxidants decreases the risk of Parkinson disease (PD).. The community-based Rotterdam Study, the Netherlands.. The cross-sectional study formed part of a large community-based study in which all participants were individually screened for parkinsonism and were administered a semiquantitative food frequency questionnaire. The study population consisted of 5342 independently living individuals without dementia between 55 and 95 years of age, including 31 participants with PD (Hoehn-Yahr stages 1-3).. The odds ratio for PD was 0.5 (95% confidence interval [CI], 0.2-0.9) per 10-mg daily dietary vitamin E intake, 0.6 (95% CI, 0.3-1.3) per 1-mg beta carotene intake, 0.9 (95% CI, 0.4-1.9) per 100-mg vitamin C intake, and 0.9 (95% CI, 0.7-1.2) per 10-mg flavonoids intake, all adjusted for age, sex, smoking habits, and energy intake. The association with vitamin E intake was dose dependent (P for trend = .03). To assess whether the association was different in participants with more advanced disease, we excluded those with PD who had a Hoehn-Yahr stage of 2.5 or 3. This did not fundamentally alter the results.. Our data suggest that a high intake of dietary vitamin E may protect against the occurrence of PD.

Topics: Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Cross-Sectional Studies; Diet; Female; Flavonoids; Humans; Male; Middle Aged; Netherlands; Odds Ratio; Parkinson Disease, Secondary; Severity of Illness Index; Surveys and Questionnaires; Vitamin E

The effects of the Parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were evaluated in four different monkey brain areas (frontal and occipital cortex, caudate putamen, substantia nigra). The basal and stimulated lipid peroxidation and the reduced glutathione (GSH) concentration were evaluated in three groups of male Macaca fascicularis monkeys (6 animals/group): (a) controls; (b) MPTP-treated animals; (c) animals treated with MPTP and alpha-dihydroergocryptine (DEK; ergot alkaloid characterized by a dopaminergic agonist action). In MPTP-treated animals the GSH concentration was unchanged or decreased in a non-significant way in the frontal and occipital cortex, and in substantia nigra. The basal thiobabituric acid reactive substance (TBARS) concentrations were significantly higher in the caudate putamen and substantia nigra of MPTP-treated animals. In the MPTP-treated monkeys the DEK administration induced a restoration of basal TBARS values to nearly normal ones. By incubating tissue from different brain areas with FeSO4 plus ascorbic acid, the stimulation of lipid peroxidation decreased the TBARS production in the substantia nigra of the MPTP-treated animals. These results, taken together, may indicate that an increased lipid peroxidation could possibly play a role in producing the Parkinson-like syndrome by MPTP and that a free radical excess could be responsible for the degeneration of the substantia nigra. The treatment with an ergot alkaloid (i.e., alpha-dihydroergocryptine) partially antagonizes the MPTP-induced increase in basal TBARS concentration in caudate putamen.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Ascorbic Acid; Brain; Caudate Nucleus; Dihydroergotoxine; Ferrous Compounds; Frontal Lobe; Glutathione; Lipid Peroxidation; Macaca fascicularis; Male; Occipital Lobe; Oxidation-Reduction; Parkinson Disease, Secondary; Putamen; Substantia Nigra; Thiobarbituric Acid Reactive Substances

Topics: Ascorbic Acid; Dopamine; Dopamine Antagonists; Humans; Manganese Poisoning; Oxidation-Reduction; Parkinson Disease, Secondary