Hebrew University and Ben-Gurion researchers find that stress causes shift in gene products

Jerusalem, January 16, 2002 We all know that traumatic experiences may be followed by long periods of nervousness and over-sensitive responses to signals that would not otherwise raise a response. What we do not know is how that happens, how experience translates into neurological changes that persist even after a considerable lapse of time. Researchers at The Hebrew University of Jerusalems Roland Center for Neurodegenerative Diseases and at Ben-Gurion University, in work on experimental mice, have now found evidence, which will be published on January 18 in the prestigious American journal Science, for the fact that stress causes a shift in gene products (mRNAs) by altered splicing, the normal cut and paste mechanism that modifies mRNA. Key features of the brain are extremely elaborate networks of nerve cells (neurons), connected through long, branched extensions that reach out to neighboring neurons. Structures (synapses) found at the ends of these extensions, are the connections between neurons of the same network. mRNAs transmit the information from genes to the apparatus in which proteins are made, so altered splicing results in different proteins being made. Stress causes changes in the splicing of many gene products, particularly in neurons, which has the result of modifying key neuronal proteins. In particular, the ACHE gene, whose protein product, acetylcholinesterase, helps control signaling across synapses between one neuron and another, produces a normally rare mRNA following trauma.

At HU, Eran Meshorer, a Ph.D. candidate, working in collaboration with Dr. Nissim Ben-Arie and Roi Gazit, another a Ph.D. candidate, found that following stress, unlike the usual mRNA product of ACHE, this new mRNA moves into the long extensions of neurons. The stress-induced mRNA produces an unusual variant of the acetylcholinesterase protein, a protein that, unlike the usual protein, cannot be integrated into synapses to assists transmission of nerve impulses. Thi

Contact: Heidi Gleit
The Hebrew University of Jerusalem

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