Splice this: End-to-end annealing demonstrated in neuronal neurofilaments

While popularly publicized neuroscience research focuses on structural and functional connectomes, timing patterns of axonal spikes, neural plasticity, and other areas of inquiry, the intraneuronal environment also receives a great deal of investigative attention.

One example is the study of cytoskeletal polymers called neurofilaments –intermediate filaments of nerve cells that and a major component of the neuronal cytoskeleton believed to provide the axon with structural support. Neurofilaments are transported into axons where they accumulate during development, causing the axons to expand in girth. This is important because the cross-sectional area of an axon influences the rate of propagation of the nerve impulse. The space-filling properties of these polymers are maximized by spoke-like projection domains called side-arms that function to space the polymers apart. Once in the axons these polymers (which are barely 10 nm in diameter) can grow to reach remarkably long lengths – 100,000 nm (0.1 mm) or more – but how they attain such lengths and how their length is regulated is not known. Recently, scientists at The Ohio State University – who previously showed that neurofilaments and vimentin filaments expressed in nonneuronal cell lines can lengthen by joining ends in a process known as end-to-end annealing – demonstrated robust and efficient end-to-end annealing of neurofilaments in nerve cells. In additions, the researchers reported evidence for a neurofilament-severing mechanism.

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Vision restored with total darkness

Restoring vision might sometimes be as simple as turning out the lights. That’s according to a study reported on February 14 in Current Biology, a Cell Press publication, in which researchers examined kittens with a visual impairment known as amblyopia before and after they spent 10 days in complete darkness.

Researchers Kevin Duffy and Donald Mitchell of Dalhousie University in Canada believe that exposure to darkness causes some parts of the visual system to revert to an early stage in development, when there is greater flexibility.

"There may be ways to increase brain plasticity and recover from disorders such as amblyopia without drug intervention," Duffy says. "Immersion in total darkness seems to reset the visual brain to enable remarkable recovery."

Amblyopia affects about four percent of the general population and is thought to develop when the two eyes do not see equally well in early life, as the connections from the eyes to visual areas in the brain are still being refined. Left untreated, that imbalance of vision can lead to permanent vision loss.

In the new study, the researchers examined kittens with amblyopia induced by experimentally depriving them of visual input to one eye. After those animals were plunged into darkness, their vision made a profound and rapid recovery. Further examination suggested that the restoration of vision depends on the loss of neurofilaments that hold the visual system in place. With those stabilizing elements gone, the visual system becomes free to correct itself.

Darkness therapy holds promise for the treatment of children with amblyopia, the researchers say, but don’t try this at home. They think that the darkness must be absolute to work, with no stray light at any time. It is also important to address the original cause of the amblyopia first, and to ensure that a period of darkness will not harm an individual’s good eye.

The researchers are still working out just how much darkness is required, and for how long. Regardless, they say it is unlikely that a drug could ever adequately mimic the effects of darkness that they’ve seen.

"The advantage of a simple nonpharmacological sensory manipulation, such as a period of darkness, is that it may initiate changes in a constellation of molecules in a beneficial temporal order and in appropriate brain regions," they write.