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Hebrew University And Ben-Gurion Researchers Find That Stress Causes Shift In Gene Products

Date:
January 21, 2002
Source:
Hebrew University Of Jerusalem
Summary:
Researchers at The Hebrew University of Jerusalem’s Roland Center for Neurodegenerative Diseases and at Ben-Gurion University, in work on experimental mice, have now found evidence for the fact that stress causes a shift in gene products (mRNAs) by altered splicing, the normal cut and paste mechanism that modifies mRNA.
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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 Jerusalem’s 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. This raised the question of whether synapses located on these neurons would be able to normally transmit signals from one neuron to another.

As these impulses can be detected as electrical activity in the brain, at BGU Dr. Alon Friedman and Lev Pavlovski, a Ph.D. candidate there, measured this electrical activity in mice weeks after the mice were exposed to stress. They found much greater activity in the brains of stressed mice than in non-stressed mice. Drs. David Glick, Christina Erb (a Minerva Foundation fellow) and Daniela Kaufer also contributed to the study.

“Our study shows that stress initiates a series of events that includes changes in mRNA splicing and a consequent change of a key protein in neurons that results in an oversensitive electrical response,” says Prof. Hermona Soreq, who headed the research team.

Patients who receive drugs that affect their nervous systems may eventually benefit from the recognition that stress renders them more sensitive to these drugs. Furthermore, the findings direct attention to altered mRNAs as targets for a new class of drugs, which is the focus of efforts at Ester Neuroscience, Ltd., which also supported the study. The study also was supported by the U.S. Army, the U.S.-Israel Binational Science Foundation and the European Community.


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The above post is reprinted from materials provided by Hebrew University Of Jerusalem. Note: Materials may be edited for content and length.


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Hebrew University Of Jerusalem. "Hebrew University And Ben-Gurion Researchers Find That Stress Causes Shift In Gene Products." ScienceDaily. ScienceDaily, 21 January 2002. <www.sciencedaily.com/releases/2002/01/020118075319.htm>.
Hebrew University Of Jerusalem. (2002, January 21). Hebrew University And Ben-Gurion Researchers Find That Stress Causes Shift In Gene Products. ScienceDaily. Retrieved September 3, 2015 from www.sciencedaily.com/releases/2002/01/020118075319.htm
Hebrew University Of Jerusalem. "Hebrew University And Ben-Gurion Researchers Find That Stress Causes Shift In Gene Products." ScienceDaily. www.sciencedaily.com/releases/2002/01/020118075319.htm (accessed September 3, 2015).

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