title: Learning performances and vulnerability to amyloid toxicity in the butyrylcholinesterase knockout mouse.
abstract: Butyrylcholinesterase (BChE) is an important enzyme for detoxication and metabolism of ester compounds. It also hydrolyzes the neurotransmitter acetylcholine (ACh) in pathological conditions and may play a role in Alzheimer's disease (AD). We here compared the learning ability and vulnerability to Aβ toxicity in male and female BChE knockout (KO) mice and their 129Sv wild-type (Wt) controls. Animals tested for place learning in the water-maze showed increased acquisition slopes and presence in the training quadrant during the probe test. An increased passive avoidance response was also observed for males. BChE KO mice therefore showed enhanced learning ability in spatial and non-spatial memory tests. Intracerebroventricular (ICV) injection of increasing doses of amyloid-β[25-35] (Aβ25-35) peptide oligomers resulted, in Wt mice, in learning and memory deficits, oxidative stress and decrease in ACh hippocampal content. In BChE KO mice, the Aβ25-35-induced deficit in place learning was attenuated in males and blocked in females. No change in lipid peroxidation or ACh levels was observed after Aβ25-35 treatment in male or female BChE KO mice. These data showed that the genetic invalidation of BChE in mice augmented learning capacities and lowered the vulnerability to Aβ toxicity.
authors: Université Montpellier, F-34095 Montpellier, France; Inserm U1198, F-34095 Montpellier, France; EPHE, F-75014 Paris, France; Amylgen, F-34980 Montferrier-sur-Lez, France. Electronic address: maurice@univ-montp2.fr.
authors: Tangui
authors: T
authors: Maurice
authors: Université Montpellier, F-34095 Montpellier, France; Inserm U1198, F-34095 Montpellier, France; EPHE, F-75014 Paris, France.
authors: Manon
authors: M
authors: Strehaiano
authors: Amylgen, F-34980 Montferrier-sur-Lez, France.
authors: Nathalie
authors: N
authors: Siméon
authors: Université Montpellier, F-34095 Montpellier, France; INRA UMR866, F-34060 Montpellier, France.
authors: Christelle
authors: C
authors: Bertrand
authors: Université Montpellier, F-34095 Montpellier, France; INRA UMR866, F-34060 Montpellier, France.
authors: Arnaud
authors: A
authors: Chatonnet
mesh_terms: D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D002091:Butyrylcholinesterase / Q000235:genetics / Q000502:physiology*; D003072:Cognition Disorders / Q000139:chemically induced* / Q000503:physiopathology; D005260:Female; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000008:administration & dosage / Q000633:toxicity*; D012737:Sex Factors; D065853:Spatial Learning / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D002091:Butyrylcholinesterase
keywords: Alzheimer’s disease; Amyloid toxicity; Butyrylcholinesterase; Knockout mice; Learning and memory