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

• Published in: Science (American Association for the Advancement of Science) Vol. 295; no. 5554; pp. 508 - 512
• Main Authors: Meshorer, Eran, Erb, Christina, Gazit, Roi, Pavlovsky, Lev, Kaufer, Daniela, Friedman, Alon, Glick, David, Ben-Arie, Nissim, Soreq, Hermona
• Format: Journal Article
• Language: English
• Published: United States American Society for the Advancement of Science 18.01.2002; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Acetylcholine - metabolism; Acetylcholinesterase - genetics; Acetylcholinesterase - metabolism; Action Potentials; Alternative Splicing; Animals; Atropine - pharmacology; Cells, Cultured; Cerebellum - cytology; Cholinesterase Inhibitors - pharmacology; Corticosterone; Corticosterone - pharmacology; Cultured cells; Dendrites; Genes; Hippocampus - cytology; Hippocampus - metabolism; Hippocampus - physiology; Hypersensitivity; In Situ Hybridization, Fluorescence; In Vitro Techniques; Messenger RNA; Mice; Mice, Transgenic; Neurites; Neurites - metabolism; Neurons; Neurons - metabolism; Neuroscience; Oligonucleotides, Antisense - pharmacology; Pain; PC12 Cells; Physiological aspects; Physostigmine - pharmacology; Post-traumatic stress disorder; Posttraumatic Stress Disorder; Proteins; Rats; Ribonucleic acid; RNA; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stress; Stress, Physiological - genetics; Stress, Physiological - physiopathology; Time Factors; Transcripts (Written Records)
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1066752

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.