1.A Rat Model of Striatonigral Degeneration Generated by Simultaneous Injection of 6-Hydroxydopamine into the Medial Forebrain Bundle and Quinolinic Acid into the Striatum.
Hyung Ho YOON ; Yong Hwan KIM ; Eun Sil SHIN ; Sang Ryong JEON
Journal of Korean Medical Science 2014;29(11):1555-1561
A double toxin-double lesion strategy is well-known to generate a rat model of striatonigral degeneration (SND) such as multiple system atrophy-parkinsonian type. However, with this model it is difficult to distinguish SND from Parkinson's disease (PD). In this study, we propose a new rat model of SND, which is generated by simultaneous injection of 6-hydroxydopamine into the medial forebrain bundle and quinolinic acid into the striatum. Stepping tests performed 30 min after intraperitoneal L-dopa administration at 6 weeks post-surgery revealed an L-dopa response in the PD group but not the SND group. Apomorphine-induced rotation tests revealed no rotational bias in the SND group, which persisted for 2 months, but contralateral rotations in the PD group. MicroPET scans revealed glucose hypometabolism and dopamine transporter impairment on the lesioned striatum in the SND group. Tyrosine hydroxylase immunostaining in the SND group revealed that 74.7% of nigral cells on the lesioned side were lost after lesion surgery. These results suggest that the proposed simultaneous double toxin-double lesion method successfully created a rat model of SND that had behavioral outcomes, multitracer microPET evaluation, and histological aspects consistent with SND pathology. This model will be useful for future study of SND.
Animals
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Apomorphine/pharmacology
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Behavior, Animal/drug effects
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Corpus Striatum/drug effects/pathology
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Disease Models, Animal
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Dopamine Plasma Membrane Transport Proteins/metabolism
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Glucose/metabolism
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Injections, Intraperitoneal
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Levodopa/pharmacology
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Male
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Medial Forebrain Bundle/drug effects/pathology
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Oxidopamine/*toxicity
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Parkinson Disease/metabolism/pathology
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Positron-Emission Tomography
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Quinolinic Acid/*toxicity
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Rats
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Rats, Wistar
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Striatonigral Degeneration/*chemically induced/metabolism/pathology
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Touch/drug effects
2.Electroacupuncture Alleviates Motor Symptoms and Up-Regulates Vesicular Glutamatergic Transporter 1 Expression in the Subthalamic Nucleus in a Unilateral 6-Hydroxydopamine-Lesioned Hemi-Parkinsonian Rat Model.
Yanyan WANG ; Yong WANG ; Junhua LIU ; Xiaomin WANG
Neuroscience Bulletin 2018;34(3):476-484
Previous studies have shown that electroacupuncture (EA) promotes recovery of motor function in Parkinson's disease (PD). However the mechanisms are not completely understood. Clinically, the subthalamic nucleus (STN) is a critical target for deep brain stimulation treatment of PD, and vesicular glutamate transporter 1 (VGluT1) plays an important role in the modulation of glutamate in the STN derived from the cortex. In this study, a 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD was treated with 100 Hz EA for 4 weeks. Immunohistochemical analysis of tyrosine hydroxylase (TH) showed that EA treatment had no effect on TH expression in the ipsilateral striatum or substantia nigra pars compacta, though it alleviated several of the parkinsonian motor symptoms. Compared with the hemi-parkinsonian rats without EA treatment, the 100 Hz EA treatment significantly decreased apomorphine-induced rotation and increased the latency in the Rotarod test. Notably, the EA treatment reversed the 6-OHDA-induced down-regulation of VGluT1 in the STN. The results demonstrated that EA alleviated motor symptoms and up-regulated VGluT1 in the ipsilateral STN of hemi-parkinsonian rats, suggesting that up-regulation of VGluT1 in the STN may be related to the effects of EA on parkinsonian motor symptoms via restoration of function in the cortico-STN pathway.
Adrenergic Agents
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toxicity
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Animals
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Apomorphine
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pharmacology
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Disease Models, Animal
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Dopamine Agonists
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pharmacology
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Electroacupuncture
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methods
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Functional Laterality
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drug effects
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Male
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Medial Forebrain Bundle
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injuries
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Motor Activity
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drug effects
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physiology
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Neurons
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drug effects
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metabolism
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Oxidopamine
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toxicity
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Parkinson Disease, Secondary
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chemically induced
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physiopathology
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therapy
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Rats
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Rats, Sprague-Dawley
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Subthalamic Nucleus
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drug effects
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metabolism
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pathology
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Tyrosine 3-Monooxygenase
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metabolism
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Up-Regulation
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drug effects
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physiology
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Vesicular Glutamate Transport Protein 1
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metabolism