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Science 18 January 2002:
Vol. 295. no. 5554, pp. 508 - 512
DOI: 10.1126/science.1066752
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Reports

Alternative Splicing and Neuritic mRNA Translocation Under Long-Term Neuronal Hypersensitivity

Eran Meshorer, Christina Erb, Roi Gazit, Lev Pavlovsky, Daniela Kaufer,* Alon Friedman, David Glick, Nissim Ben-Arie, Hermona Soreqdagger

To explore neuronal mechanisms underlying long-term consequences of stress, we studied stress-induced changes in the neuritic translocation of acetylcholinesterase (AChE) splice variants. Under normal conditions, we found the synaptic AChE-S mRNA and protein in neurites. Corticosterone, anticholinesterases, and forced swim, each facilitated a rapid (minutes), yet long-lasting (weeks), shift from AChE-S to the normally rare AChE-R mRNA, promoted AChE-R mRNA translocation into neurites, and induced enzyme secretion. Weeks after stress, electrophysiological measurements in hippocampus slices displayed apparently normal evoked synaptic responses but extreme hypersensitivity to both anticholinesterases and atropine. Our findings suggest that neuronal hypersensitivity under stress involves neuritic replacement of AChE-S with AChE-R.

Departments of 1Biological Chemistry and 2Cell and Animal Biology, The Institute of Life Sciences and The Eric Roland Center for Neurodegenerative Diseases, The Hebrew University of Jerusalem, Israel 91904. 3Departments of Physiology and Neurosurgery, Zlotowsky Center of Neuroscience, Ben Gurion University and Soroka Medical Center, Beersheva, Israel 84105.
*   Present address: Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.

dagger    To whom correspondence should be addressed. E-mail: soreq{at}shum.huji.ac.il

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