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National Antivisection Society

Case study: research using marmoset monkeys funded by Parkinsons UK

Posted: 13 December 2011. Updated: 6 November 2012

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Zeng, B-Y. et al (2010) “Morphological changes in serotoninergic neurites in the striatum and globus pallidus in levodopa primed MPTP treated common marmosets with dyskinesia. “,Neurobiology of Disease, vol. 40, pp: 599 – 607

Parkinson’s UK is the operating name of the Parkinson’s Disease Society of the United Kingdom.

Common marmosets were brain damaged with a chemical neurotoxin (MPTP) (1) which causes Parkinson’s-like syndrome and the induction of jerky and impaired movement was caused using a current Parkinson’s therapy (Levodopa), which leads to motor complications with long term use (2). The aim was to see if these treatments alter the appearance of fibres related to the transmission of serotonin in a specific region of the brain.

Twelve animals were used, 8 of which were treated with the MPTP and 4 were also chronically treated with the Parkinson’s therapy to induce motor complications Animals were killed at the end of the study, and their brains removed for analysis.

Repetition:

The authors explain that similar experimental models have previously shown that the effects of a chemical, which activates serotonin, prevent dyskinesia (a lack of control of voluntary movement], in rats which were brain damaged with a different neurotoxin(3). They also state that their findings support previous experimental data gained in rodents “that the serotoninergic system plays an important role in dyskinesia”.

Other researchers identified the serotonin system as an emerging key element in the development of motor complications induced by long-term treatment in parkinsonian rats and monkeys (4). Therefore, this work does not appear to contribute further to knowledge regarding induced parkinsonian syndromes in animal models.

Species differences and awareness of them:

The researchers do not address the differences between human and primate physiology, nor the limitations of artificially inducing Parkinson’s disease in primates through the use of MPTP. Parkinson’s disease does not develop spontaneously in any animals except humans. Toxin-based Parkinson’s models (such as that in the current study) are limited in their usefulness as disease symptoms manifest rapidly or immediately following dosage of the toxin (5), in contrast to the actual disease which develops gradually over a period of time. A review of non-human primate models of Parkinson’s noted “the various methods of inducing parkinsonism in monkeys affect the characteristics of the syndrome”, and “The choice of monkey species in which to model the disease affects the research”. Furthermore, “one model cannot replicate the complex and individual variability of PD” (1). The authors do not mention these limitations.

Current available treatments:

There is currently no cure for Parkinson’s disease. Treatments are available to help control the symptoms and maintain quality of life. These include supportive therapy such as physiotherapy, occupational therapy, speech and language therapy, and dietary changes; numerous medicines to control the symptoms including levodopa (often combined with other medication i.e. carbidopa), and surgery such as deep brain stimulation (2) The current study however, is focussed upon the mechanisms of dyskinesia induction in MPTP treated marmosets using levodopa and carbidopa, and not the development of a new treatment in itself.

Animal suffering:

MPTP was administered to marmosets to induce a “syndrome of stable motor deficits”. MPTP treated animals exhibited “marked hypokinesia [decreased body movement] and pronounced motor disability.” Four of the MPTP treated animals that were then subjected to acute treatment with levodopa went on to display “profound involuntary movements”, despite an improvement in motor disability.

Clearly the onset of these symptoms had the potential to cause great suffering to previously healthy animals. They will have undergone a rapid degeneration in their health and experienced a loss of control of their movements over the period of the experiment. The marmosets were also hand fed a high protein/carbohydrate liquid diet for 8-10 weeks during the experimental period, indicating that animals were initially unable to feed independently following MPTP administration, an indication of the severity of its effects. A review of non-human primate models of Parkinson’s disease noted that “The general effects of MPTP or the resulting difficulty moving may cause animals to decrease their food and fluid intake and therefore lose weight” (1) At the end of the study, animals were killed via anaesthetic overdose, and their brains removed for analysis.

Alternative advance techniques:

A 2003 study used SPECT (single-photon emission computed tomography), a non-invasive imaging technology to study neuronal integrity in the degenerative process of Parkinson’s, in 45 patients with the disease (6). Non-invasive imaging studies in humans allow researchers to follow disease progression, and to monitor different stages of pathology. This is in contrast to the current study which analysed brain slices in animals, representing snap-shots of a single point in time.

Poor experimental planning:

The authors note that 12 animals, male and female were used in the study, however do not specify how many of each sex were used. They note that the animals were housed “singly or in pairs”, but do not specify which, or how many animals were housed in each manner, or the reasons for the difference. MPTP was administered at 2.0mg/kg daily for 5 consecutive days. However it has been noted by others with regard to this method of dosing that “Although acute systemic administration can induce a PD syndrome in 4 to 5 days, its main limitations are severe animal debilitation and lack of predictability” (1). These limitations are not mentioned by the authors.

Disease context:

Parkinson’s disease is a long-term neurological condition that affects around 120,000 people in the UK. Around 10,000 people are diagnosed with the condition each year. (7)

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References

1.Emborg, M.E. (2007) “Nonhuman Primate Models of Parkinson’s Disease”, ILAR Journal, vol. 48, 4, 339-355
2.http://www.nhs.uk/Conditions/Parkinsons-disease/Pages/Treatment.aspx - Accessed 10/10/11
3.Muñoz, A. et al. (2009) “Serotonin neuron-dependent and –independent reduction of dyskinesia by 5-HT1A and 5-HT1B receptor agonists in the rat Parkinson model”, Experimental Neurology, vol. 219, 298-307.
4.Muñoz, A. et al. (2009) “Serotonin neuron-dependent and –independent reduction of dyskinesia by 5-HT1A and 5-HT1B receptor agonists in the rat Parkinson model”, Experimental Neurology, vol. 219, 298-307.
5.Potashkin, J.A. et al. (2011) “Limitations of Animal Models of Parkinson’s Disease”, Parkinson’s Disease, Volume 2011, Article ID 658083, doi:10.4061/2011/658083,
6.Eun Kim, S. et al. (2003) “Serotonin Transporters in the Midbrain of Parkinson’s Disease Patients: A Study with 123I-β-CIT SPECT”, The Journal of Nuclear Medicine, vol. 44, 6, 870-876.
7.http://www.nhs.uk/Conditions/Parkinsons-disease/Pages/Introduction.aspx - Accessed 04/10/11.

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