An automated movement assessment panel for upper limb motor functions in rhesus monkeys and humans

Gash, Don M.; Zhang, Zhiming; Umberger, Gloria; Mahood, Kim; Smith, Melody; Smith, Charles D.; Gerhardt, Greg A.

doi:10.1016/s0165-0270(99)00051-5

Cited by 45 publications

(41 citation statements)

References 11 publications

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“…To evaluate motor function before and after MPTP treatment, we used a monkey movement assessment panel that evaluates manual dexterity based on ability and time to retrieve a ''lifesaver'' treat by using the left (affected) hand from one of three locations: a platform, a straight rod, or a hook (26). The most complex task required a unique sequence of wrist and hand movements to maneuver a small round food reward over a rod curved like a hook before removing it from a small acrylic receptacle.…”

Section: Resultsmentioning

confidence: 99%

“…The time of treat retrieval (recorded from sensors attached to the panel) and also the ability of each monkey to retrieve treats from three levels of difficulty (platform, straight rod, and hook) were noted from the weekly testing procedure described in ref. 26. Monkeys received preliminary shaping on the task before their diet group assignments and then received formal training 6-10 weeks before MPTP treatment, and beginning 7 weeks afterward, they were tested every other week over a 10-week period.…”

Section: Mptp Treatmentmentioning

confidence: 99%

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Caloric restriction increases neurotrophic factor levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson's disease

Maswood

Young

Tilmont

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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We report that a low-calorie diet can lessen the severity of neurochemical deficits and motor dysfunction in a primate model of Parkinson's disease. Adult male rhesus monkeys were maintained for 6 months on a reduced-calorie diet [30% caloric restriction (CR)] or an ad libitum control diet after which they were subjected to treatment with a neurotoxin to produce a hemiparkinson condition. After neurotoxin treatment, CR monkeys exhibited significantly higher levels of locomotor activity compared with control monkeys as well as higher levels of dopamine (DA) and DA metabolites in the striatal region. Increased survival of DA neurons in the substantia nigra and improved manual dexterity were noted but did not reach statistical significance. Levels of glial cell linederived neurotrophic factor, which is known to promote the survival of DA neurons, were increased significantly in the caudate nucleus of CR monkeys, suggesting a role for glial cell line-derived neurotrophic factor in the anti-Parkinson's disease effect of the low-calorie diet.brain-derived neurotrophic factor ͉ cell death ͉ dopamine P arkinson's disease (PD) results from the dysfunction and degeneration of dopamine (DA) neurons in the substantia nigra (SN) and DA axon terminals, resulting in progressive motor dysfunction (1). The risk of PD increases with advancing age, suggesting that cellular and molecular changes that occur in the brain during normal aging may promote the degeneration of DA neurons. In this regard, increased oxidative stress and impaired energy metabolism and protein turnover occur in DA neurons during normal aging, and these changes are greatly exacerbated in PD (2, 3). Although a small number of cases of PD result from inherited genetic mutations in one of three genes, ␣-synuclein, Parkin, or DJ-1 (4), most cases are sporadic with an unknown environmental cause(s). Nevertheless, studies of genetic and neurotoxin-based animal models of PD point to the involvement of oxidative stress and impaired energy metabolism and protein turnover in the pathogenesis of PD (3-6). There is currently no established intervention to prevent, or decrease the risk of, PD.Most studies of humans have concluded that a decrease in the number of DA neurons in the SN occurs during normal aging, with PD being an acceleration of this process (7-9). However, some investigators have reported no age-related decline in the number of DA neurons (10). Studies in rhesus monkeys have been more consistent in reporting age-related decline in the number of tyrosine hydroxylase (TH)-positive SN neurons (11, 12). However, because some monkey studies have reported increased numbers of THpositive nigral neurons after treatment with neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), an age-related decline in expression of TH could be an alternative explanation to the results suggesting an age-related loss of nigral neurons (13).In a wide range of laboratory animals, caloric restriction (CR) has been shown to prolong lifespan, decrease the incid...

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Section: Resultsmentioning

confidence: 99%

Section: Mptp Treatmentmentioning

confidence: 99%

Caloric restriction increases neurotrophic factor levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson's disease

Maswood

Young

Tilmont

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

346

243

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“…In the current primate study, contralateral improvement may have been the first signs of graft function. To objectively determine ipsilateral and contralateral function in non-human primates would have required the use of tests specifically designed to analyze motor performance of both sides independently (Gash et al, 1999;Jenkins et al, 2004). The PRS and ADL behavioral scales used in the present study were not designed to measure side bias.…”

Section: Discussionmentioning

confidence: 99%

Influence of cell preparation and target location on the behavioral recovery after striatal transplantation of fetal dopaminergic neurons in a primate model of Parkinson’s disease

Redmond¹,

Viñuela

Kordower

et al. 2008

Neurobiology of Disease

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Surgeries involving transplantation of fetal dopamine (DA) neurons into the caudate-putamen of patients with Parkinson's disease (PD) have been performed in various clinical trials to examine a potential restoration of motor function. The absence of studies in nonhuman primates to define the best transplantation protocols have lead to the use of a broad variety of techniques that potentially could have a major impact on the clinical outcome. The effects of using different cell and tissue preparation, and surgical targets, remain unknown. For this purpose, 20 St. Kitts African Green Monkeys (AFG) rendered parkinsonian by i.m injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), were balanced into 4 groups and unilaterally grafted in the (a) caudate or (b) putamen with fetal ventral mesencephalic (VM) tissue as (c) solid pieces or as a (d) cell suspension. By 9 months post-transplantation all animals showed significant and similar behavioral improvement as determined by an UPDRS based PD scale. Postmortem analyses showed that VM transplants survived in all animals. They were located in both surgical target sites, producing a broad DA reinnervation of the targeted nuclei that could also extend to the non-grafted nucleus on the ipsilateral side. Although no differences between groups were found in survival of DA neurons or degree of DA reinnervation, there was a significant correlation between striatal reinnervation and behavioral recovery only in animals transplanted in the putamen surgical target. Additionally, there was in general, a stronger glial reaction to solid grafts than to cell suspensions. These studies provide data for the optimal time-course, cell preparation and surgical targets for systematic examinations of both potential benefits and side effects of dopamine neuron cell transplantation in primate models of PD.

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“…The testing protocol was in accordance with the previous report of Gash et al (1999). All monkeys were well adapted to the panel and were retrieving food regularly within 3-5 days before the formal testing, and there were no feeding was 3 h in advance of each test.…”

Section: Animalsmentioning

confidence: 99%

“…Age-associated declines in motor behavior in primates include impairment in arm movement, locomotion activity, and motor skill tasks (Gerhardt et al 1995;Ovadia et al 1995;Emborg et al 1998;Gash et al 1999;Grondin et al 2000;Zhang et al 2000Zhang et al , 2001Grondin et al 2003;Lacreuse et al 2005). It has been suggested that for the overall evaluation of motor behaviors in nonhuman primates, the two following aspects should be involved: activity monitoring for quantitative assessment of the total amount of movement activity over a certain duration, and the assessment of motor skill tasks in order to accurately measure the upper limb's coarse and fine movement times (Emborg 2004).…”

Section: Introductionmentioning

confidence: 99%

Age-related decline in motor behavior and striatal dopamine transporter in cynomolgus monkeys

Yue

Zeng

et al. 2012

J Neural Transm

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Advanced human aging is associated with progressive declines of motor function and a risk factor for Parkinson's disease, which mainly involves central nigrostriatal dopaminergic system. The present study investigated age-related changes in motor behaviors and alterations of the number of nigrostriatal dopaminergic terminals in non-human primates. A total of 30 cynomolgus monkeys (Macaca fascicularis) of age 3.5-15.5 years were studied. Motor behaviors including upper limb movement time and the amount of overall home cage activity were quantitatively assessed using a modified movement assessment panel and a newly developed webcam-based monitoring system. The function of the dopaminergic system was semi-quantitatively measured by (99m)Tc-TRODAT-1 uptake rates, a dopamine transporter (DAT) specific radiopharmaceutical with SPECT imaging. The results showed a significant decline in motor behaviors associated with aging which were significantly correlated with age-related decreases of (99m)Tc-TRODAT-1 uptake. A further partial correlation analysis independent of age indicated that age contributed to the relationship between striatal DAT levels and motor behaviors. Our results indicate that normal aging-related dopamine physiology influences certain aspects of motor behaviors and suggest that aging-associated dysfunction in the nigrostriatal dopaminergic system may be an important factor contributing to the decline of motor behaviors in aging cynomolgus monkeys.

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An automated movement assessment panel for upper limb motor functions in rhesus monkeys and humans

Cited by 45 publications

References 11 publications

Caloric restriction increases neurotrophic factor levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson's disease

Caloric restriction increases neurotrophic factor levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson's disease

Influence of cell preparation and target location on the behavioral recovery after striatal transplantation of fetal dopaminergic neurons in a primate model of Parkinson’s disease

Age-related decline in motor behavior and striatal dopamine transporter in cynomolgus monkeys

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