Acetylcholinesterase knockouts establish central cholinergic pathways and can use butyrylcholinesterase to hydrolyze acetylcholine

M. M. Mesulam, A. Guillozet, P. Shaw, A. Levey, E. G. Duysen, Oksana Lockridge

Research output: Contribution to journalArticle

418 Citations (Scopus)

Abstract

Acetylcholinesterase is one of the most prominent constituents of central cholinergic pathways. It terminates the synaptic action of acetylcholine through hydrolysis and yields the choline moiety that is necessary for transmitter recycling. Despite these pivotal relationships, mice nullizygous for acetylcholinesterase established all principal anatomical components of central cholinergic pathways. No compensatory increase in the distribution of butyrylcholinesterase was detected. However, both the wild-type and nullizygous mice showed that butyrylcholinesterase enzyme activity extended to all parts of the brain receiving cholinergic innervation and that it could hydrolyze the acetylcholine surrogate acetylthiocholine. As opposed to acetylcholinesterase which was mostly of neuronal origin, butyrylcholinesterase appeared to be mostly of glial origin. These experiments lead to the unexpected conclusion that acetylcholinesterase is not necessary for the establishment of cholinergic pathways. They also show that butyrylcholinesterase can potentially substitute for acetylcholinesterase and that this enzyme is likely to play a constitutive (rather than just back-up) role in the hydrolysis of acetylcholine in the normal brain. The inhibition of butyrylcholinesterase may therefore provide a desirable feature of cholinergic therapies, including those aimed at treating Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)627-639
Number of pages13
JournalNeuroscience
Volume110
Issue number4
DOIs
StatePublished - Apr 3 2002

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Butyrylcholinesterase
Acetylcholinesterase
Cholinergic Agents
Acetylcholine
Hydrolysis
Acetylthiocholine
Brain
Recycling
Enzymes
Choline
Neuroglia
Alzheimer Disease

Keywords

  • Alzheimer's disease
  • Basal forebrain
  • Cerebral cortex
  • Choline acetyltransferase
  • Striatum

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Acetylcholinesterase knockouts establish central cholinergic pathways and can use butyrylcholinesterase to hydrolyze acetylcholine. / Mesulam, M. M.; Guillozet, A.; Shaw, P.; Levey, A.; Duysen, E. G.; Lockridge, Oksana.

In: Neuroscience, Vol. 110, No. 4, 03.04.2002, p. 627-639.

Research output: Contribution to journalArticle

Mesulam, M. M. ; Guillozet, A. ; Shaw, P. ; Levey, A. ; Duysen, E. G. ; Lockridge, Oksana. / Acetylcholinesterase knockouts establish central cholinergic pathways and can use butyrylcholinesterase to hydrolyze acetylcholine. In: Neuroscience. 2002 ; Vol. 110, No. 4. pp. 627-639.
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