The Right Tools for the JobPredicting Which Cells Will Go
Does ALS affect all motor neurons equally? Investigator Jonathan Glass (Emory U, Atlanta) knows the answer is no. His studies show that, as in humans with ALS, some motor neurons in SOD1 animal models stay healthy, even until the animal’s death. This year, Glass proposed a way to tag motor neurons bound for decline, based on an antibody’s response. Now he and colleague Jean-Pierre Julien (Laval U., Quebec) are trying to explain the basis for the variable antibody response. Knowing that could help understand what keeps some cells alive. They suspect that natural changes with age may tip certain cells into vulnerability. A Model of Its Kind
An expert in the pathology of the nervous system, John Griffin (Johns Hopkins) has bemoaned the lack of a clean, easy way to follow ALS changes in motor neurons. Having such a tool is a key to tracking the true success of therapies and understanding how they work. Now, he and his team have singled out a motor nerve in model mice that's of useful length and position as a disease monitor, one with easily-visible nerve/muscle junctions. The lateral thoracic nerve runs down the back and flank of model mice and is handily dissected and stained for study. Readying the Gene Report
Though the technique is complex, the underlying idea isn’t: Find out which genes are normally turned on in young, healthy mice and compare that with what’s on and what’s off in ALS model mice of the same age. Such early study, even before the animals develop symptoms, could help pinpoint the cause of ALS. This year, Maiken Nedergaard (U. of Rochester) has shown it’s possible to monitor overall gene activity in key spinal cord cells of healthy mice and of SOD1 mouse models destined to develop ALS symptoms. More Than Motor Neurons
Motor neurons aren’t the only cells in the nervous system involved in ALS. Astrocytes, specifically, can advance ALS, says Nicholas Maragakis (Johns Hopkins). But, so far, there’s no easy way to observe how that happens. To remedy that, Maragakis developed a new study system, using stem cells that typically create astrocytes. He transplants the immature astrocyte cells—they also carry the SOD1 ALS gene—into rats’ spinal cords. The result is a spinal cord mix of ALS-primed diseased astrocytes and normal motor neurons. The work isn’t yet published, so all we can say is that our scientists are indeed interested as Maragakis monitors the rats for disease symptoms. | 
