ReviewMarmoset monkey models of Parkinson's disease: Which model, when and why?
Section snippets
What is Parkinson's disease and what are the different marmoset models of the disorder?
In the UK alone, an estimated 11,000 people per year will be diagnosed with Parkinson's disease (PD), joining approximately 120,000 people who already suffer from the disorder [67]. The cardinal clinical features of the disease involve a motor dysfunction that manifests itself as tremor, muscular rigidity, bradykinesia, akinesia and postural instability [28]. Psychiatric and cognitive symptoms, such as depression and working memory deficits, can also be observed [1], [75]. The underlying
Why are marmosets a useful species for PD research?
Experimental use of monkeys is an important intermediary between rodent studies and controlled clinical trials when the phylogenetic similarity to humans is pivotal for the efficacy of the treatment [90]. There are subtle but significant differences between rodents and monkeys/humans in the anatomical structures involved in the pathology of PD, which may have important implications for treatment strategy and functional outcome. These differences include, for example, the fact that in monkeys
Why use MPTP models in the marmoset?
MPTP was discovered to be a dopaminergic neurotoxin in the early 1980s after the synthetic heroin injected by several young Californian drug users was contaminated with the substance [62]. These addicts displayed the cardinal features of the idiopathic disease including bradykinesia, rigidity, and in some cases, resting tremor [8]. Post-mortem analysis demonstrated that there was neuronal cell loss relatively specific for cells in the Substantia Nigra pars compacta (SNpc; [8]). The mechanism
Why use 6-OHDA models in the marmoset?
6-OHDA is a neurotoxin specific for catecholamine cells including DA cells. It was first used by Ungerstedt in the late 1960s to target DA cells [95]. The neurotoxic effect of 6-OHDA is mediated by its similarity in structure to the catecholamines. This similarity is thought to contribute to its uptake into catecholamine neurons via specific re-uptake transporters, thus acting as a “false transmitter” [89]. In DA neurons, 6-OHDA is taken up by the DA transporter (DAT) and once in the cell,
Why use selective α-synuclein over-expression in the marmoset?
The connection between abnormalities in the processing of the pre-synaptic protein α-synuclein and PD was first recognized by Polymeropoulos et al. [80] with the discovery that a point mutation in the α-synuclein gene was associated with an early onset autosomal dominant form of the disease in an Italian family and three unrelated Greek families. Soon after, Spillantini et al. [91] demonstrated that α-synuclein was a major component of Lewy bodies in PD patients. In its normal physiological
Which PD marmoset model is best for assessing novel treatments?
The pharmaceutical industry follows a sequence of stages for the development of treatments for human diseases. The initial stages of treatment development are often the identification of a specific target structure involved in the pathological process and the production of a candidate drug that interacts with that target. The next stages of development include the determination of the efficacy of the treatment in animal models, prior to its assessment in humans. Primate models play an important
Future development of marmoset models of PD: where do we go from here?
Insight into the aetiology of PD may provide the basis for future models. For example, the evidence that the ubiquitin–proteasome system may be dysfunctional in PD suggests a possible model that involves disruption to this system. There are also potentially useful models which have been investigated in rodents but not yet in marmosets. The pesticide rotenone falls into this category and has been shown to induce DA cell death by interrupting mitochondrial function (for review see [33]). Genetic
Acknowledgements
The author would like to thank Rosalind Ridley, Harry Baker and David Virley for their critical reading of the manuscript.
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