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Near‐complete adaptation of the PRiMA knockout to the lack of central acetylcholinesterase
Author(s) -
Farar Vladimir,
Mohr Franziska,
Legrand Marie,
Lamotte d’Incamps Boris,
Cendelin Jan,
Leroy Jacqueline,
Abitbol Marc,
Bernard Veronique,
Baud Frédéric,
Fournet Vincent,
Houze Pascal,
Klein Jochen,
Plaud Benoit,
Tuma Jan,
Zimmermann Martina,
Ascher Philippe,
Hrabovska Anna,
Myslivecek Jaromir,
Krejci Eric
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2012.07856.x
Subject(s) - acetylcholinesterase , aché , acetylcholine , medicine , endocrinology , muscarinic acetylcholine receptor , extracellular , chemistry , biology , receptor , biochemistry , enzyme
J. Neurochem . (2012) 122 , 1065–1080. 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.