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Brain May Compensate for Dopamine Neuron Loss Early in Parkinsonís

Scientists estimate that by the time a person develops the hallmark Parkinson’s disease (PD) symptoms, such as tremor or slowness, at least 25 percent of the brain’s dopamine neurons already have been lost.  So why do symptoms not become apparent sooner?  The answer, according to an opinion letter published in the March 25 issue of Neurology, may lie in the brain’s ability to compensate for the loss of dopamine neurons early in PD.  

In previous research with animal models of PD, scientists have found clues as to how the brain might overcome the loss of dopamine neurons. In rats and mice with PD-like symptoms that have lost dopamine neurons, researchers have observed that the remaining dopamine neurons eventually sprout new connections and release more dopamine, making up for the cells that have died and, most importantly, alleviating symptoms. 

What’s puzzling, however, is that the structure of those newly sprouted connections is abnormal – they sometimes connect with the wrong location. Scientists asked: how can neurons that make so many wrong connections still be heard? 

Authors David Arkadir, M.D. Ph.D., a recently trained movement disorder fellow from the PDF’s fellowship program at the PDF Research Center at Columbia University Medical Center along with PDF’s Scientific Director, Stanley Fahn, M.D., and Hagai Bergman, M.D., Ph.D., from Hebrew University, Jerusalem, Israel, speculated what might be happening.


  • The scientists propose that the newly sprouted connections, despite making many wrong connections, are still able to communicate appropriately because the cells (healthy and sick) are all sending the same, redundant signal – like the voices in a choir all singing the same note.  
  • For a time, adding new connections or “voices” to this choir can make up for the death of other dopamine neurons. 
  • After a time, the authors speculate that PD symptoms appear because the new connections can no longer keep pace and maintain dopamine signaling as the disease progresses and more neurons die.

What Does It Mean?

Currently, this is only a hypothesis proposed by Drs. Arkadir, Bergman, and Fahn.  Nevertheless, new ideas on how Parkinson’s disease progresses are essential to move the field forward.  Ideas like these can be experimentally-tested in order to be proven or disproven. 

What are the implications of this hypothesis?  The authors suggest that the actions the brain takes to compensate for Parkinson’s – the growth of new connections and production of more dopamine – may come at a price that could actually hasten the progression of the disease.  They suggest that early treatment with levodopa (Sinemet®) therapy may be able to boost dopamine production and relieve the burden on dopamine neurons, which could explain why people treated earlier with levodopa experience a higher quality of life for a longer period of time.  

However, no one has yet observed the new connections dopamine neurons make in people with Parkinson’s.  There are also alternative explanations for how the brain may compensate for dopamine neuron loss. But by generating ideas about how Parkinson’s disease progresses that can, in turn, be tested, a better understanding will develop that can help guide the search for therapies that slow PD progression.  

Reference: Arkadir D, Bergman H, Fahn S (2014) Redundant dopaminergic activity may enable compensatory axonal sprouting in Parkinson disease. Neurology 82:1093–1098. DOI: 10.1212/WNL.0000000000000243

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Source Date: May 12 2014