Posts Tagged ‘central nervous system’

Whether it’s on a keyboard, a smartphone, or even a credit card reader, you spend a lot of your day typing. Well, researchers at MIT noticed the value of this daily habit, and are putting it to a secondary use; they’ve developed software that can gauge the speed at which a typist is tapping the keyboard to help diagnose Parkinson’s disease.

In order to type a word, your brain has to send signals down through your spinal cord to the nerves that operate your fingers. If your central nervous system is functioning perfectly, then you should be able to tap most of the keys at a fairly constant rate. But a number of conditions might slow the signal from the brain to the fingers, such as sleep deprivation (which slows all motor skills) and diseases that affect the central nervous system, including Parkinson’s.

For the first version of this study, the researchers were looking at typing patterns that indicated whether a person was sleep-deprived or well rested. They created a browser plug-in that detected the timing at which the volunteers hit they keys and found that the people who were sleepy had a much wider variation in their typing speed. They found similar results in their preliminary test with Parkinson’s patients; the 21 typists with Parkinson’s tapped the keys at much more variable rates than the 15 healthy volunteers. The researchers called it a “window into the brain.”

Right now, the algorithm they’ve developed is not refined enough to distinguish Parkinson’s patients from people who are sleep deprived, though the results might be clearer after a number of trials. The researchers plan to conduct a study with a larger group of subjects, but they hope that this type test could eventually lead to earlier diagnoses of Parkinson’s–today most people are diagnosed after they have had symptoms for 5-10 years–and to distinguish Parkinson’s from other conditions that might affect a person’s motor skills, like rheumatoid arthritis. They are currently developing a smartphone app that can test participants even more easily.

The mechanisms that drive axon regeneration after central nervous system (CNS) injury or disease are proposed to recapitulate, at least in part, the developmental axon growth pathways. This hypothesis is bolstered by a new study by O’Donovan et al. showing that activation of a B-RAF kinase signaling pathway is sufficient to promote robust axon growth not only during development but also after injury.

B-RAF was previously shown to be essential for developmental axon growth but it was not known if additional signaling pathways are required. In this study, the authors demonstrate that activation of B-RAF alone is sufficient to promote sensory axon growth during development. Using a conditional B-RAF gain-of-function mouse model, the authors elegantly prove that B-RAF has a cell-autonomous role in the developmental axon growth program. Notably, activated B-RAF promoted overgrowth of embryonic sensory axons projecting centrally in the spinal cord, suggesting that this pathway may normally be quiescent in central axons.

Could activated B-RAF also enhance axon regeneration in the adult central nervous system? The authors found that activated B-RAF not only enabled sensory axon growth into the spinal cord after spinal injury, but also promoted regrowth of axons projecting in the optic nerve. Regeneration in the injured CNS is prevented by both the poor intrinsic regrowth capacity of axons and by inhibitory factors in the tissue environment. Importantly, the B-RAF–activated signaling growth program was insensitive to this repulsive environment.

Interestingly, the authors find that B-RAF synergizes with the PI3-kinase–mTOR pathway, which also functions downstream of growth factors. This opens the possibility that combinatorial approaches that integrate these two pathways may heighten regenerative capacity.

This in vivo study significantly advances the understanding of the role of MAP kinases in axon growth and suggests that reactivation of the B-RAF pathway may be exploited to promote axon regeneration in the injured central nervous system. An exciting future avenue will be to determine the downstream mechanisms controlled by B-RAF.

O’Donovan, K.J., et al. 2014. J. Exp. Med. doi:10.1084/jem.20131780.