The researchers found that Parkinson's disease arises in complex neurons with lots of branches that demand high levels of energy.
This was the finding of a new study led by researchers at the University of Montreal in Canada reported in the journal Current Biology.
The researchers have spent the last 17 years studying the part of the brain that causes Parkinson's disease, schizophrenia and drug addiction, say:
"Like a motor constantly running at high speed, these neurons need to produce an incredible amount of energy to function. They appear to exhaust themselves and die prematurely."
The researchers hope the findings will produce better ways to represent Parkinson's disease in animal models and lead to new treatments. It is very difficult to reproduce symptoms of Parkinson's disease in mice, even when you insert human genes into their genomes.
This could then lead to discovery of drugs to help brain cells reduce their energy consumption or use energy more efficiently, thus reducing the damage they accumulate over time. The team is already pursuing this end.
Parkinson's disease arises from the death of brain cells in a few restricted areas of the brain, such as the substantia nigra. The brain cells affected by Parkinson's disease release dopamine, a chemical messenger that helps to regulate movement, emotional responses and other functions.
As the disease progresses, the amount of dopamine produced in the brain decreases and the symptoms - which include tremor, slowness, stiffness and impaired balance - gradually worsen, making it increasingly difficult to walk, talk, look after oneself and have a normal life.
Mitochondria 'forced to work at burnout rates'
For the last 3 years, the team has been investigating why the mitochondria inside cells in the areas of the brain affected by Parkinson's disease work so hard and overheat. Mitochondria are tiny powerhouses that produce the energy cells need to function, grow and release signals.
Fast facts about Parkinson's disease
- An estimated 7-10 million people worldwide are living with Parkinson's disease
- Men are 1.5 times more likely to have Parkinson's than women
- Each person with Parkinson's will experience symptoms differently.
They discovered that the cells in these brain areas have very complex structures with lots of branches and sites where the chemical messengers are released, and suggest it is this complexity that demands high levels of energy.
The researchers explain that their findings support the idea that these complex neurons force their mitochondria to work at burnout rates to meet their energy demands, which would explain their accelerated deterioration.
"To use the analogy of a motor," he says, "a car that overheats will burn significantly more fuel, and, not surprisingly, end up at the garage more often."
As we age, this complexity may also make the brain cells particularly vulnerable - they are more likely to malfunction and die, triggering Parkinson's disease, a condition that predominantly strikes later in life.
As life expectancy increases, so does the challenge to find treatments for neurodegenerative diseases like Parkinson's, since:
"From an evolutionary standpoint, some of our neurons are perhaps just not programmed to last 80, 90 or 100 years, as we are seeing more and more. It's to be expected that certain parts of our body are less able to withstand the effects of time."
But the researchers are hopeful that because Parkinson's disease only affects a limited part of the brain, effective treatments will be found sooner rather than later.
References:
1. Elevated mitochondrial bioenergetics and axonal arborization size are key contributors to the vulnerability of dopamine neurons, Consiglia Pacelli et al., Current Biology, doi: 10.1016/j.cub.2015.07.050, published online 27 August 2015, abstract.
2. Université de Montréal news release, accessed 28 August 2015.
3. Additional source: Parkinson's Disease Foundation, What is Parkinson’s Disease?, accessed 28 August 2015.
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