Alternative splicing and neuritic mRNA translocation under long-term neuronal hypersensitivity.
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.
Meshorer
Eran
E
Department of Biological Chemistry, The Institute of Life Sciences and The Eric Roland Center for Neurodegenerative Diseases, The Hebrew University of Jerusalem, Israel 91904.
Erb
Christina
C
Gazit
Roi
R
Pavlovsky
Lev
L
Kaufer
Daniela
D
Friedman
Alon
A
Glick
David
D
Ben-Arie
Nissim
N
Soreq
Hermona
H
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
D002800:Cholinesterase Inhibitors; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D001285:Atropine; D010830:Physostigmine; D000110:Acetylcholinesterase; D000109:Acetylcholine; D003345:Corticosterone