Overexcited neurons not good for c...(increase in Parkinsons disease and other...)

Neuronal Signaling Modulates Protein Homeostasis in Caenorhabditis Elegans Post-synaptic Muscle Cells is published by the journal Genes & Development. In addition to Morimoto, the studys co-investigators include lead author Susana M. Garcia, a former graduate student of Morimotos and now a postdoctoral fellow at Harvard University; M. Olivia Casanueva, a postdoctoral fellow, and M. Catarina Silva, a visiting predoctoral student, both at Northwestern; and Margarida D. Amaral, University of Lisbon, Portugal.

Morimoto and his team studied presynaptic neurons and postsynaptic muscle cells in C. elegans, a transparent roundworm whose biochemical environment is similar to that of human beings and whose genome, or complete genetic sequence, is known.

Specifically, the researchers looked at what happened to polyglutamine proteins in muscle cells that were at the tipping point: the proteins were at risk of soon aggregating and losing their function. The scientists wanted to see if they could cause the protein, which is associated with Huntingtons disease, to show its toxicity prematurely. (If misfolded or damaged proteins accumulate beyond a certain critical point, they aggregate and disease can result. )

In separate experiments, the researchers induced two genetic mutations in presynaptic neurons, one that caused the reduction of the neurotransmitter GABA, which inhibits neuronal firing, and one that increases the action of a neurotransmitter called acetylcholine, which stimulates neuronal firing. The result of both mutations was overexcited neurons that disrupted the way the neurons sent signals to the muscle cells and caused protein aggregation.

The effects were similar when the researchers introduced both nicotine (a neurostimulant) and lindane (an inhibitor of GABA, c
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