Developing a stable bilateral model of parkinsonism in rhesus monkeys

Smith, R. D.; Zhang, Z.; Kurlan, Roger; McDermott, Michael P.; Gash, Don M.

doi:10.1016/0306-4522(93)90176-g

Cited by 98 publications

(60 citation statements)

References 22 publications

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“…Old rhesus monkeys (over 23 years of age) which had been injected with MPTP (0.4mg/kg) bilaterally into the cerebral artery similarly developed a stable Parkinsonian syndrome which persisted up to a maximum of 45 days after the lesion. A 95% loss of total motor activity could still be demonstrated 12 months after the lesion (Smith et al, 1993). In neither experiments no neurochemical analyse were performed, thus it is not possible to comment on the neurochemical correlation of this functional disturbance.…”

Section: Neurotoxic Actionmentioning

confidence: 92%

“…The precise appearance of symptoms varies, depending on the species, age and dosage. MPTP-syndromes have been described, among others, in rhesus monkeys (Burns et al, 1983;Smith et al, 1993), in squirrel monkeys (Irwin et al, 1990), in macaques (Crossman et al, 1989), in baboons (Hantraye et al, 1993) and above all in marmosets (Ueki et al, 1989;Russ et al, 1991). The quantitation of the symptoms in monkeys is achieved using modified PD scales.…”

Section: Behavioural Changesmentioning

confidence: 98%

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Animal models of Parkinson's disease: An empirical comparison with the phenomenology of the disease in man

Gerlach

Riederer

1996

J. Neural Transmission

443

221

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Animal models are an important aid in experimental medical science because they enable one to study the pathogenetic mechanisms and the therapeutic principles of treating the functional disturbances (symptoms) of human diseases. Once the causative mechanism is understood, animal models are also helpful in the development of therapeutic approaches exploiting this understanding. On the basis of experimental and clinical findings. Parkinson's disease (PD) became the first neurological disease to be treated palliatively by neurotransmitter replacement therapy. The pathological hallmark of PD is a specific degeneration of nigral and other pigmented brainstem nuclei, with a characteristic inclusion, the Lewy body, in remaining nerve cells. There is now a lot of evidence that degeneration of the dopaminergic nigral neurones and the resulting striatal dopamine-deficiency syndrome are responsible for its classic motor symptoms akinesia and bradykinesia. PD is one of many human diseases which do not appear to have spontaneously arisen in animals. The characteristic features of the disease can however be more or less faithfully imitated in animals through the administration of various neurotoxic agents and drugs disturbing the dopaminergic neurotransmission. The cause of chronic nigral cell death in PD and the underlying mechanisms remain elusive. The partial elucidation of the processes underlie the selective action of neurotoxic substances such as 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), has however revealed possible molecular mechanisms that give rise to neuronal death. Accordingly, hypotheses concerning the mechanisms of these neurotoxines have been related to the pathogenesis of nigral cell death in PD. The present contribution starts out by describing some of the clinical, pathological and neurochemical phenomena of PD. The currently most important animal models (e.g. the reserpine model, neuroleptic-induced catalepsy, tremor models, experimentally-induced degeneration of nigrostriatal dopaminergic neurons with 6-OHDA, methamphetamine, MPTP, MPP+, tetrahydroisoquinolines, beta-carbolines, and iron) critically reviewed next, and are compared with the characteristic features of the disease in man.

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Section: Neurotoxic Actionmentioning

confidence: 92%

Section: Behavioural Changesmentioning

confidence: 98%

Animal models of Parkinson's disease: An empirical comparison with the phenomenology of the disease in man

Gerlach

Riederer

1996

J. Neural Transmission

443

221

View full text Add to dashboard Cite

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“…The Guide for the Care and Use of Laboratory Animals (National Academy Press,1996) was followed. The animals' behavior was evaluated on a parkinsonian monkey rating scale which consists of tremor, posture, gait, bradykinesia, balance, gross motor skills, and defense reactions (total score = 20) [11]. In each surgical session, the monkeys were sedated with ketamine hydrochloride (10 mg/kg b.wt., i.m.)…”

Section: Methodsmentioning

confidence: 99%

The Role of the Pedunculopontine Tegmental Nucleus in Experimental Parkinsonism in Primates

Matsumura

Kojima²

2001

Stereotact Funct Neurosurg

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To clarify the role of the pedunculopontine tegmental nucleus (PPN) in motor behavior, we have conducted a series of experiments in primates. In the first part, PPN was damaged locally with kainic acid, which resulted in mild hemiparkinsonism in the contralateral limbs. In the second part, muscimol (a GABA agonist) was locally injected into the PPN area in monkeys who had been trained to perform a lever-pull movement with an arm, resulting in a slowness of movement and a delay of the movement onset. In the third part, a dopaminergic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was systemically injected in monkeys with prior PPN lesioning. These monkeys developed no, or if any, very mild parkinsonism. PPN lesioning was supposed to have protected the nigral neurons from the MPTP- toxicity. The PPN facilitates the motor system through its nigral projection. The decreased activity of the PPN may underlie the pathophysiology of parkinsonism.

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“…All animals received right intracarotid artery infusion of MPTP (0.4mg/kg) to induce continuously expressed advanced hemi-parkinsonism ( (10,11). Prior to the present study, the animals had also been used in a GDNF dose response study (12).…”

Section: Animalsmentioning

confidence: 99%

Globus pallidus plays a critical role in neurotrophic factor induced functional improvements in hemiparkinsonian monkeys

Xin

Gerhardt

et al. 2008

Biochemical and Biophysical Research Communications

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This study was designed to test the hypothesis that the integrity of the globus pallidus (GP) is critical for neurotrophic factor, such as glial-derived neurotrophic factor (GDNF), induced functional changes in rhesus macaques with MPTP-induced parkinsonism, because our previous studies demonstrated that the GP was one of the most affected areas as assessed by the levels of dopamine (DA) and its metabolites. A group of 8 hemiparkinsonian monkeys with pallidal lesions, which positively responsed to intraventricular (ICV) injections of GDNF prior to the lesions, and a group of 8 hemiparkinsonian monkeys without pallidal lesions, were treated with GDNF after a long washout period after the initial ICV infusions of GDNF. Significant behavioral improvements were only seen in the monkeys without pallidal lesions that received GDNF. Monkeys with pallidal lesions failed to exhibit any behavioral improvement even though they had elevated nigral DA levels. The results suggest that the GP is critical for neurotrophic factor induced functional changes in PD monkeys.

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Developing a stable bilateral model of parkinsonism in rhesus monkeys

Cited by 98 publications

References 22 publications

Animal models of Parkinson's disease: An empirical comparison with the phenomenology of the disease in man

Animal models of Parkinson's disease: An empirical comparison with the phenomenology of the disease in man

The Role of the Pedunculopontine Tegmental Nucleus in Experimental Parkinsonism in Primates

Globus pallidus plays a critical role in neurotrophic factor induced functional improvements in hemiparkinsonian monkeys

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