P.1.d.026 Nicotine ameliorates behavioural deficits and oxidative stress in a 6-hydroxydopamine rat model of Parkinson's disease

Parkinson's disease (PD) is one of the major neurodegenerative disorders, and oxidative stress has been implicated in playing an important role in the pathogenesis of the disease. In the present study, we investigated if Delphinium denudatum extract can slow down the neuronal injury in 6-hydroxydopamine (6-OHDA) rat model of Parkinsonism. Rats were treated with 200, 400 and 600 mg/kg body weight (b.w.) of D. denudatum extract for 3 weeks. On day 22, 2 mL of 6-OHDA (10 mgin 0.1% ascorbic acid-saline) or vehicle was infused into the right striatum of the animals. Three weeks after the 6-OHDA injections, the rats were killed for estimation of lipid peroxidation (LPO), reduced glutathione (GSH) content, superoxide dismutase (SOD) and catalase (CAT) activities, catecholamines, dopaminergic D2 receptor binding and tyrosine hydroxylase (TH) expression. Increased LPO and significant depletion of reduced GSH content in the substantia nigra resulting from the lesion were appreciably prevented with Delphinium treatment. Delphinium extract also dose-dependently attenuated the activities of SOD and CAT in striatum, which had been reduced significantly by lesioning. A significant decrease in the level of dopamine (DA) and its metabolites and an increase in the number of dopaminergic D2 receptors in striatum were observed after 6-OHDA injection, both parameters were significantly recovered with treatment of the extract. Finally, all these results were confirmed by an increase in expression of TH in the ipsilateral striatum of the lesioned groups following treatment with Delphinium extract. Thus, the study indicates that D. denudatum extract may be helpful in checking neuronal injury in Parkinsonism.

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PW01-81 - Deficits of spatial memory and oxidative stress damage following exposure to lipopolysaccharide in a rat model of Parkinson's disease

European Psychiatry ◽

10.1016/s0924-9338(10)71480-2 ◽

2010 ◽

Vol 25 ◽

pp. 1497

Author(s):

L. Hritcu ◽

A. Ciobica ◽

M. Stefan ◽

T. Nabeshima

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Spatial Memory ◽

Rat Model ◽

Stress Damage ◽

And Oxidative Stress

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Are Proteinopathy and Oxidative Stress Two Sides of the Same Coin?

Cells ◽

10.3390/cells8010059 ◽

2019 ◽

Vol 8 (1) ◽

pp. 59 ◽

Cited By ~ 4

Author(s):

Nihar Mehta ◽

Praneet Marwah ◽

David Njus

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Protein Aggregation ◽

Great Majority ◽

Protein Aggregates ◽

Oxidation Products ◽

Full Picture ◽

6 Hydroxydopamine ◽

And Oxidative Stress

Parkinson’s disease, like other neurodegenerative diseases, exhibits two common features: Proteinopathy and oxidative stress, leading to protein aggregation and mitochondrial damage respectively. Because both protein aggregates and dysfunctional mitochondria are eliminated by autophagy, we suggest that inadequate clearance may couple the two phenomena. If a neuron’s autophagy machinery is overwhelmed, whether by excessive oxidative stress or by excessive protein aggregation, protein aggregates and dysfunctional mitochondria will both accumulate. Parkinson’s disease may provide a unique window into this because there is evidence that both sides contribute. Mutations amplifying the aggregation of α-synuclein are associated with Parkinson’s disease. Likewise, mutations in Parkin and PINK1, proteins involved in mitophagy, suggest that impaired mitochondrial clearance is also a contributing factor. Many have suggested that dopamine oxidation products lead to oxidative stress accounting for the dopaminergic selectivity of the disease. We have presented evidence for the specific involvement of hypochlorite-oxidized cysteinyl-dopamine (HOCD), a redox-cycling benzothiazine derivative. While toxins like 6-hydroxydopamine and 1-methyl-4-phenyl pyridinium (MPP+) have been used to study mitochondrial involvement in Parkinson’s disease, HOCD may provide a more physiologically relevant approach. Understanding the role of mitochondrial dysfunction and oxidative stress in Parkinson’s disease and their relation to α-synuclein proteinopathy is important to gain a full picture of the cause, especially for the great majority of cases which are idiopathic.

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Effects of right-unilateral 6-hydroxydopamine infusion-induced memory impairment and oxidative stress: relevance for Parkinson’s disease

Open Life Sciences ◽

10.2478/s11535-008-0023-8 ◽

2008 ◽

Vol 3 (3) ◽

pp. 250-257 ◽

Cited By ~ 16

Author(s):

Lucian Hritcu ◽

Alin Ciobica ◽

Vlad Artenie

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Memory Impairment ◽

Short Term Memory ◽

Term Memory ◽

Shuttle Box ◽

Y Maze ◽

6 Hydroxydopamine ◽

And Oxidative Stress

AbstractMale Wistar rats were subjected to right-unilateral 6-hydroxydopamine (6-OHDA) (2 μg/μl) lesions of the ventral tegmental area (VTA) or the substantia nigra (SN), or were sham-operated, and their ability to acquire the operant task was studied by means of Y-maze and shuttle-box tasks. Lesions of both the VTA and the SN resulted in an impairment of conditioned avoidance response and increase of crossing latency tested by means of shuttle-box task, suggesting significant effects of long-term memory. 6-OHDA significantly decreased spontaneous alternation in Y-maze task, suggesting effects on spatial memory, especially on short-term memory. In addition, 6-OHDA lesions of the VTA and the SN induced reductions in superoxide dismutase (SOD), glutathione peroxidase (GPX) activities and malondialdehyde (MDA) levels in the temporal lobe rather than in the frontal lobe homogenates. Our results provide further support for the toxic effects of 6-OHDA-induced memory impairment and oxidative stress with relevance for Parkinson’s disease.

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