title: Acetylcholinesterase modulates stress-induced motor responses through catalytic and noncatalytic properties.
abstract: BACKGROUND
  Cholinergic neurotransmission notably participates in stress-induced motor responses. Here we report the contribution of alternative splicing of acetylcholinesterase (AChE) pre-mRNA to modulate these responses. More specifically, we induced stress-associated hypofunction of dopaminergic, mainly D2 dopamine receptor-mediated neurotransmission by haloperidol and explored stress induced hyperlocomotion and catalepsy, an extreme form of immobility, induced in mice with AChE deficiencies.
  
  
  METHODS
  Conditional transgenic (Tet/AS) mice were created with tetracycline-induced antisense suppression of AChE gene expression. Locomotion and catalepsy times were measured in Tet/AS and strain-matched control mice, under open-field exposure threat and under home-cage safety.
  
  
  RESULTS
  In vitro, NGF-treated PC12 cells failed to extend neurites upon Tet/AS suppression. In vivo, Tet/AS but not control mice showed stress-associated hippocampal deposits of heat-shock protein 70 and GRP78 (BiP), predicting posttranscriptional changes in neuronal reactions. Supporting this notion, their striatal cholinergic neurons demonstrated facilitated capacity for neurite extension, attributing these in vivo changes in neurite extension to network interactions. Tet/AS mice presented stress-induced hyperlocomotion. Moreover, the dopamine antagonist haloperidol induced longer catalepsy in threatened Tet/AS than in control mice. When returned to home-cage safety, Tet/AS mice showed retarded release from catalepsy.
  
  
  CONCLUSIONS
  Acetylcholinesterase modulates stress-induced motor responses and facilitates resumption of normal motor behavior following stress through both catalytic and noncatalytic features.
authors.affiliation: Department of Biological Chemistry, Institute of Life Sciences, Hebrew University of Jerusalem, Givat Ram, Jerusalem, Israel.
authors.forename: Ella H
authors.initials: EH
authors.lastname: Sklan
authors.forename: Amit
authors.initials: A
authors.lastname: Berson
authors.forename: Klara R
authors.initials: KR
authors.lastname: Birikh
authors.forename: Amos
authors.initials: A
authors.lastname: Gutnick
authors.forename: Or
authors.initials: O
authors.lastname: Shahar
authors.forename: Shai
authors.initials: S
authors.lastname: Shoham
authors.forename: Hermona
authors.initials: H
authors.lastname: Soreq
mesh_terms: D000110:Acetylcholinesterase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017398:Alternative Splicing / Q000502:physiology; D000818:Animals; D002384:Catalysis / Q000187:drug effects; D002799:Cholinergic Fibers / Q000201:enzymology*; D016373:DNA, Antisense / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D000091342:Endoplasmic Reticulum Chaperone BiP; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018832:Molecular Chaperones / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology*; D017072:Neostriatum / Q000166:cytology / Q000201:enzymology; D016501:Neurites / Q000187:drug effects / Q000201:enzymology; D016716:PC12 Cells; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D013315:Stress, Psychological / Q000201:enzymology*; D013752:Tetracycline / Q000494:pharmacology
chemical_list: D016373:DNA, Antisense; D018492:Dopamine Antagonists; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D018832:Molecular Chaperones; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D000110:Acetylcholinesterase; D013752:Tetracycline; D006220:Haloperidol