title: Near-complete adaptation of the PRiMA knockout to the lack of central acetylcholinesterase.
abstract: Acetylcholinesterase (AChE) rapidly hydrolyzes acetylcholine. At the neuromuscular junction, AChE is mainly anchored in the extracellular matrix by the collagen Q, whereas in the brain, AChE is tethered by the proline-rich membrane anchor (PRiMA). The AChE-deficient mice, in which AChE has been deleted from all tissues, have severe handicaps. Surprisingly, PRiMA KO mice in which AChE is mostly eliminated from the brain show very few deficits. We now report that most of the changes observed in the brain of AChE-deficient mice, and in particular the high levels of ambient extracellular acetylcholine and the massive decrease of muscarinic receptors, are also observed in the brain of PRiMA KO. However, the two groups of mutants differ in their responses to AChE inhibitors. Since PRiMA-KO mice and AChE-deficient mice have similar low AChE concentrations in the brain but differ in the AChE content of the peripheral nervous system, these results suggest that peripheral nervous system AChE is a major target of AChE inhibitors, and that its absence in AChE- deficient mice is the main cause of the slow development and vulnerability of these mice. At the level of the brain, the adaptation to the absence of AChE is nearly complete.
authors: Centre d'Etude de la Sensorimotricité, Université Paris Descartes, CNRS UMR 8194, Paris, France.
authors: Vladimir
authors: V
authors: Farar
authors: Franziska
authors: F
authors: Mohr
authors: Marie
authors: M
authors: Legrand
authors: Boris
authors: B
authors: Lamotte d'Incamps
authors: Jan
authors: J
authors: Cendelin
authors: Jacqueline
authors: J
authors: Leroy
authors: Marc
authors: M
authors: Abitbol
authors: Veronique
authors: V
authors: Bernard
authors: Frédéric
authors: F
authors: Baud
authors: Vincent
authors: V
authors: Fournet
authors: Pascal
authors: P
authors: Houze
authors: Jochen
authors: J
authors: Klein
authors: Benoit
authors: B
authors: Plaud
authors: Jan
authors: J
authors: Tuma
authors: Martina
authors: M
authors: Zimmermann
authors: Philippe
authors: P
authors: Ascher
authors: Anna
authors: A
authors: Hrabovska
authors: Jaromir
authors: J
authors: Myslivecek
authors: Eric
authors: E
authors: Krejci
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000172:deficiency* / Q000378:metabolism; D000222:Adaptation, Physiological / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D001831:Body Temperature / Q000187:drug effects / Q000235:genetics; D001921:Brain / Q000033:anatomy & histology / Q000201:enzymology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000493:pharmacokinetics; D002038:Bungarotoxins / Q000493:pharmacokinetics; D002794:Choline / Q000378:metabolism; D018678:Cholinergic Agents / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003094:Collagen / Q000172:deficiency; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005684:Gait / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D066298:In Vitro Techniques; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D008565:Membrane Proteins / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D018727:Muscarinic Antagonists / Q000493:pharmacokinetics; D009124:Muscle Proteins / Q000172:deficiency; D009263:Nails, Ingrown; D009388:Neostigmine / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000172:deficiency*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D011485:Protein Binding / Q000187:drug effects; D011725:Pyridines / Q000493:pharmacokinetics; D011868:Radioisotopes / Q000493:pharmacokinetics; D011976:Receptors, Muscarinic / Q000378:metabolism; D045442:Rotarod Performance Test; D012601:Scopolamine / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology; D018709:Statistics, Nonparametric; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D002038:Bungarotoxins; D018678:Cholinergic Agents; D002800:Cholinesterase Inhibitors; D008565:Membrane Proteins; D018727:Muscarinic Antagonists; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D011725:Pyridines; D011868:Radioisotopes; D011976:Receptors, Muscarinic; C486718:prima1 protein, mouse; D014316:Tritium; C065959:AFDX 384; D004079:Dihydro-beta-Erythroidine; D009388:Neostigmine; D010890:Pirenzepine; D003094:Collagen; D012601:Scopolamine; D000110:Acetylcholinesterase; C534672:Colq protein, mouse; C082748:epibatidine; D002794:Choline; D000109:Acetylcholine