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The Degeneration of Dopaminergic Neurons and Changes of Inducible Nitric Oxide Synthase Induced by the Inhibitor of Proteasome

Author: CaoLiu
Tutor: NiuChaoShi;FuXianMing
School: Anhui Medical University,
Course: Surgery
Keywords: Parkinson's disease Lactacystin Dopaminergic neurons Nitric oxide synthase Substantia nigra
CLC: R742.5
Type: Master's thesis
Year: 2008
Downloads: 28
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Abstract


Objective: To observe the proteasome (proteasome) inhibitor induced movement behavior change, and dopaminergic (dopamine, DA) neuron degeneration and inducible nitric oxide synthase (inducible nitric oxidesynthase, iNOS) changes discussed proteasome The decline in the pathogenesis of Parkinson's disease (Parkinson's disease), as well as the model of the rat brain substantia nigra of inducible nitric oxide synthase in whether to participate in the proteasome inhibitor Lactacystin induced dopaminergic neuronal degeneration. Methods: (1) The proteasome inhibitor Lactacystin10μg/2μl stereotactic injection into the rat left side of the substantia nigra pars compacta, the control group was injected volume of saline; (2) observation of spontaneous behavior and apomorphine-induced rotation behavior change: (3) open field experiment rats were observed spontaneous motor behavior change detection indicators: total running time, the total settling time, the number of lower extremity standing shuttle distance, rats spontaneously to the left or right side of the line 1/4 curvature of the ring number of activities, lower limb standing left or right forelimb rely on Views Views and rats the torso the left or right side of the walls of the box near the box wall exploration activities; (4) immunohistochemical method of rat black matter region of DA neuron degeneration and different time points (1 day, 3 days, 1 week, 3 weeks) iNOS changes. Results: (1) of Lactacystin group rats administered one week after the decrease in spontaneous activity, slow movements, tremor, of the external stimuli involuntary piloerection, and the symptoms gradually worsened; apomorphine induced rotational motion to the contralateral 3 weeks after the 30 minutes of the number of rotations of 258.90 ± 11.56. (2) Lactacystin rats running time, the total settling time, lower limb standing frequency and the shuttle distance saline rats compared (p <0.05) decrease Lactacystin rats spontaneously to the left 1/4 radians ring the number of activities, lower limb standing left limb rely on the walls of the box number and rats torso near the walls of the box on the left side of the number of inquiry activities and right Compared increased (p <0.05): (3) three weeks after black The quality parts tyrosine hydroxylase (TH)-positive cells decreased. Days iNOS positive cells increased significantly, the first 3 Telsda peak and begin to decline after one week, 3 Zhou Shiji this disappear. Conclusion: The proteasome inhibitor Lactacystin10μg/2μl unilateral substantia nigra pars compacta trace injection induced black qualitative change can exhibit similar clinical symptoms of PD motor behavior change Lactacystin prepared more ideal PD animal models. The proteasome function decline may be the initiating factor of the DA neuron degeneration, iNOS raised may be of DA neuronal degeneration process.

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CLC: > Medicine, health > Neurology and psychiatry > Neurology > Brain diseases > Paralysis agitans syndrome
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