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The winner of the BRC's inaugural Discovery Grant, Dr. Turgay Akay wants to understand the underlying mechanisms of ALS (amyotrophic lateral sclerosis).

Dr. Turgay Akay wants to understand the underlying mechanisms of ALS (amyotrophic lateral sclerosis).Dr. Turgay Akay wants to understand the underlying mechanisms of ALS (amyotrophic lateral sclerosis).

“We know that people with ALS lose motor neurons, but they only start to experience deficits once they have lost a high volume of motor neurons,” says Dr. Akay, who joined Dalhousie’s Department of Medical Neuroscience from Columbia University in 2014. “This tells us that spinal circuits are extremely flexible and able to compensate for the lost motor neurons, up to a point. Perhaps we can manipulate these compensation mechanisms to preserve function and locomotion.”

Dr. Akay has applied his background in zoology, neural systems and behaviour to develop experimental models for studying ALS that are truly unique in the world. Unlike other ALS models, which involve cell cultures in Petri dishes or sacrificing mice to study their nervous tissues, Dr. Akay’s model measures muscle innervation and movement in living mice with ALS.

“To see what’s really happening in ALS, we have to observe changes in live animals throughout the entire course of the disease,” he explains. “We use electrodes to take weekly measurements on each mouse, while it is walking, running or swimming, and compare the degree of muscle innervation with the animal’s ability to move.”

Dr. Akay and his team – PhD student William Meyer and master’s student Lauren Landoni – use a measure of innervation called Compound Muscle Action Potential, or CMAP. They’ve found that a mouse’s CMAP can decline by 50 per cent with no substantial effect on walking. Only when the CMAP declines to 10 per cent and lower does the animal’s activity diminish.

“How is the muscle able to retain this much function with such low innervation? What is boosting the remaining motor neurons’ function?” asks Dr. Akay. “This could be the key to preserving function in ALS and a number of other diseases and disorders.”

He is already on the trail of a potential mechanism, a synaptic structure known as C-bouton that “turns up the volume” on motor neurons, which he discovered in 2009 with Dr. Rob Brownstone, a neurosurgeon and neuroscientist at Dalhousie Medical School.

“C-bouton is altered during ALS disease progression,” notes Dr. Akay. “The structures get larger, as they presumably work harder and harder as more motor neurons die. This, and other mechanisms, could possibly be harnessed to help people with ALS.”

Because his studies observe changes to muscle innervation and function during exercise, Dr. Akay hopes to shed light on an area of great concern to people with ALS. “Many people want to know what kind of exercise they should do, at what intensity and for how long,” he notes. “Our research will reveal a lot about the effects of exercise on innervation as ALS progresses.”

 

 

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