title: Alternative splicing and neuritic mRNA translocation under long-term neuronal hypersensitivity.
abstract: 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.
authors.affiliation: Department of Biological Chemistry, The Institute of Life Sciences and The Eric Roland Center for Neurodegenerative Diseases, The Hebrew University of Jerusalem, Israel 91904.
authors.forename: Eran
authors.initials: E
authors.lastname: Meshorer
authors.forename: Christina
authors.initials: C
authors.lastname: Erb
authors.forename: Roi
authors.initials: R
authors.lastname: Gazit
authors.forename: Lev
authors.initials: L
authors.lastname: Pavlovsky
authors.forename: Daniela
authors.initials: D
authors.lastname: Kaufer
authors.forename: Alon
authors.initials: A
authors.lastname: Friedman
authors.forename: David
authors.initials: D
authors.lastname: Glick
authors.forename: Nissim
authors.initials: N
authors.lastname: Ben-Arie
authors.forename: Hermona
authors.initials: H
authors.lastname: Soreq
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000235:genetics* / Q000378:metabolism*; D000200:Action Potentials; D017398:Alternative Splicing; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D017404:In Situ Hybridization, Fluorescence; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016716:PC12 Cells; D010830:Physostigmine / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D013312:Stress, Physiological / Q000235:genetics / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D002800:Cholinesterase Inhibitors; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D001285:Atropine; D010830:Physostigmine; D000110:Acetylcholinesterase; D000109:Acetylcholine; D003345:Corticosterone