Studying Parkinson’s Disease

Parkinson’s disease is a progressive, neurodegenerative disorder that affects six million people across the world. Symptoms of the disease become apparent with age, which means the disease primarily affects people 50 years of age and older. Certain specific genetic mutations can cause people as young as 25 to be diagnosed with Parkinson’s disease, however these forms of Parkinson’s disease are very rare. It is mostly idiopathic, meaning of unknown origin.

The symptoms caused by Parkinson’s disease, which are mainly tremors, rigidity, and postural instability, as well as cognitive decline, are caused by a loss of specific brain cells that produce a messenger substance called dopamine. Dopamine is a neurotransmitter that is secreted by cells in order to communicate with one another. When cells that produce dopamine die, there is not enough dopamine in the brain to send communications, which cause the Parkinson’s symptoms. A lot of dopamine producing cells are found in one particular area of the brain, the midbrain. The midbrain is very important for motor control, leading to the typical Parkinson’s symptoms.

Parkinson’s disease can become extremely debilitating, and because of the booming aging population, research has been focussing more on deciphering what causes the disease, and how to stop it. Animals, mainly rodents, are used to model a disease, so researchers can discover pathways and mechanisms, and use that information to stop, treat or prevent it. This involves generating an animal model that has the same defects and symptoms as the disease. Parkinson’s disease is no different – animal models are generated to have little or no dopamine producing cells, which cause the same symptoms as Parkinson’s disease. Sounds great. But, unfortunately, we don’t know why the dopamine producing cells in the midbrain die. Figuring that out is the first key step to stopping the disease from even happening. For now, there are several ways that researchers might model Parkinson’s disease, to discover methods of slowing it and treating the symptoms.

Two common ways of generating Parkinson’s disease models are through brain lesioning and genetic manipulation. Brain lesioning involves either surgically removing dopamine producing cells from the midbrain, or chemically killing these cells. In the latter, a toxic compound, that specifically only kills dopamine producing cells is injected into the brain. The problem with this is that it doesn’t model the progressive nature of the disease very well. The other method of generating rodent models with no dopamine producing cells is through genetic manipulation. Since the rare cases of a mutation of a single gene causing Parkinson’s disease are known, these genes can be targeted when making an animal model. However, if these genes are removed or altered, this can mean animals missing the genes are very young. This is not a good model for a disease that affects people in later life. So, newer gene editing technologies can be used to induce the removal or alteration of a gene at a more appropriate age. But, as with brain lesioning models, many of these gene editing techniques do not represent the progressive deterioration of the neurons.

While these methods generate animals with the symptoms Parkinson’s disease very accurately, this is not a very useful way of divining the original cause of the loss of dopamine producing cells. The hope remains that researchers will discover the root of Parkinson’s disease to finally cure it.

Did you know?

When a student attempted to generate a new and potent form of heroin, he accidentally hit upon one of the neurotoxins used to specifically kill dopamine producing cells in lesioning models. When he injected this drug, he started showing Parkinson’s symptoms, and it was later discovered that the drug contained a compound, called MPPP, which is transformed in the body to a substance called MPTP, which kills dopamine producing cells.

Review: https://doi.org/10.1016/S1353-8020(11)70057-8

About Danny Schnitzler

Danny Schnitzler is working as research assistant at the University of Edinburgh, Scotland on the role of oxytocin in feeding behaviour, while applying for PhD funding. Her scientific passion is neuroendocrinology, which looks at the role of hormones in the brain. In particular, she has an interest in how sex hormones act on neurophysiolgy. Outside of the lab, Danny is involved in addressing the gender imbalance in many aspects of STEM, public engagement and science communication. She also does "normal" fun things like going for runs, reading books and petting dogs.

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