Parkinson’s disease: From gut to brain or brain to gut?

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Taken from: https://med.stanford.edu/news/all-news/2015/12/new-technique-reveals-gut-bacteria-diversity…

In early December of last year, researchers confirmed something that had been brewing for years.  Parkinson’s disease, a degenerative brain disorder that affects motor function, may be tied to the bacteria in our gut(1).

This study took a look at the microbiome of mice prone to Parkinson’s disease and raised them in one of 2 environments:

  • A sterile environment which would make their microbiome effectively germ-free
  • A non-sterile environment which would lead to a normal microbiome

As expected, the mice in the non-sterile environment developed greater motor impairments than the ones raised in the sterile environment.  Additionally, the mice raised in the non-sterile environment were given antibiotics to  wipe out their microbiome.  This led to improvements in motor function.

This study added to the evidence that Parkinson’s disease is associated with gut issues.  It had long been considered that there was a link there since people with Parkinson’s disease often report digestive issues such as constipation a decade before motor problems occur.

A new study adds to the complex relationship between Parkinson’s and the gut.  In the previous study, the mice genetically prone to Parkinson’s get the disease because of an overproduction of a protein called alpha-synuclein.  This protein forms tangles around nerve fibers leading to the neurodegeneration seen in Parkinson’s.  These fibers are also found in the gut.

In this new study, researchers found that alpha-synuclein can travel from the brain to the stomach via the vagus nerve(2).  While it has been known that alpha-synuclein can travel from neuron to neuron, we haven’t known specifically how it travels from the brain to the gut or vice verse.

More importantly, this study showed that the alpha-synuclein traveled from the brain to the stomach via a specific type of vagus nerve fiber: efferent fibers.  Nerve fibers are typically categorized as either afferent or efferent.

Afferent nerve fibers send information about environmental conditions to the brain while efferent fibers relay a motor response to the organ or muscles.  In this way, afferent fibers communicate sensory information from an organ to the brain and efferent fibers communicate the response from the brain to the organ.  For an organ to work properly, both types of fibers must function properly.  “Tangles” in efferent nerve fibers cause problems by not relaying the appropriate response from brain to organ.

For example, you’re probably aware of the reflex that occurs when you hit your knee with a hammer.  Sensors in the knee relay a message to the brain via afferent fibers and the brain sends instructions back to muscles in the leg to contract.  This causes you to kick.  A problem with afferent fibers means the brain doesn’t get the message, but a problem with efferent fibers means the brain gets the message but the response isn’t communicated to the muscles.

In terms of the gut, this means that the stomach is sensing things properly and the brain is getting the message.  But when the brain relays what to do to the stomach the message gets lost.  This effects motility of the stomach and would have far-reaching implications throughout the gut.

Neither of these studies identify where the problem originates.  Based solely on this most recent study, the implication is that this specific mechanism originates in the brain and travels to the gut.  Only 20% of vagus nerve fibers are efferent, and there was no evidence that alpha-synuclein traveled via afferent fibers.

Ultimately, what we have is a clearer yet still incomplete picture.  There’s a relationship between the gut and Parkinson’s disease, but where the problem originates is still up in the air.  Hopefully, future evidence will drive us in the right direction.

 

 

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