Research Areas:

Parkinson's Disease

With approximately 7 million people suffering from Parkinson’s disease (PD) world-wide it is one of the most frequent age-related diseases of the central nervous system. PD is caused by the death of neurons in a part of the brain that controls movement. This damage results in the typical motoric symptoms, such as shaking, rigidity or slowness of movement. Other symptoms include sleep disturbance, depression and dementia. At this moment there is no cure for PD.

Because most PD-patients only seek medical attention after the disease has progressed, early event of the disease cannot be studied in humans. BPRC has a well-characterized experimental model of PD in a monkey, the common marmoset. PD is induced by repeated injections of MPTP, which is converted into a toxic metabolite MMP+. MMP+ is selectively taken up in (dopaminergic) motor neurons and blocks the cell’s energy production. Marmosets injected with MPTP develop characteristic non-motor (sleep disturbance) and motor symptoms.

PD research at BPRC is focused on understanding the processes that contributes to the pathology and clinical expression of the disease. Our model is used for the development of pharmaceutical and non-pharmaceutical therapies that stop the neurodegenerative process, suppress disease symptoms and prevent side effects of the current medications.

Compensation by the Red Nucleus may explain why primates can develop stable Parkinson’s disease

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BPRC identified a new target to manage Parkinsonian symptoms. This approach focuses on a part of the brain called the “red nucleus”. This red nucleus controls movement in quadrupedal animals (animals that walk on four legs, like rodents and cats), and it also regulates the crawling movement in babies until other areas of the brain then take over. It is known that the red nucleus in PD is enlarged compared to non-PD people. Presumably because the red nucleus gets activated to compensate for affected parts of the brain.

Our researchers examined whether the same phenomenon could be observed in monkey models of PD. Their findings showed that animals with a larger red nucleus displayed fewer Parkinson’s symptoms than animals with a smaller red nucleus. In addition, stimulation of this compensatory pathway seemed to increase the size of the red nucleus even more. The study also focused on a part of the red nucleus that mainly occurs in humans and primates. Though a different part of the red nucleus is active in quadrupeds, it is striking to note that these animals can spontaneously recover from PD symptoms, whereas this is not observed in primates. This is yet another indication that the red nucleus may be very important.

The information from this study is currently being prepared for publication and will be published in 2019.

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Refinement of the MPTP model for the induction of Parkinson’s disease in the marmoset monkey

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The MPTP-model in common marmoset monkey is frequently used for PD research. However, there is still a debate about the level of discomfort in this model.

BPRC has performed a meta-analysis to identify the most optimal induction protocol minimizing discomfort for the monkey. This resulted in a refinement of our MPTP marmoset model by lowering the dosage and increasing the interval of MPTP administration. The new approach minimizes the interference of direct effects of the toxin MPTP on clinical signs that may have an impact on the animal and the outcome of the results. It also reduces the discomfort for the animal as the progression of the clinical features develop more slowly over time, which also mimicks the human counterpart of PD.

Finetuning of the MPTP-induction protocol may, therefore, improve the well-being of the animal and development of rational, effective treatments for the multifactorial pathogenic mechanisms of PD.

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