Learning performances and vulnerability to amyloid toxicity in the butyrylcholinesterase knockout mouse

Maurice, Tangui; Strehaïano, Manon; Siméon, N.; Bertrand, Christelle; Chatonnet, Arnaud

doi:10.1016/j.bbr.2015.08.026

Cited by 58 publications

(55 citation statements)

References 53 publications

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“…This fact must be considered carefully when interpreting outcomes, especially in purely observational studies. Shortly after our aggression data were published, however, Chatonnet’s group released a study focused on cognitive function in BChE-knockout and wild type mice [27]. Their report included a statement that they were “unable to confirm” our observations on mouse aggression.…”

Section: Introductionmentioning

confidence: 99%

Physiological roles for butyrylcholinesterase: A BChE-ghrelin axis

Brimijoin

Chen

Pang

et al. 2016

Chemico-Biological Interactions

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Butyrylcholinesterase (BChE) has long been regarded as an “orphan enzyme” with no specific physiological role other than to metabolize exogenous bioactive esters in the diet or in medicines. Human beings with genetic mutations that eliminate all BChE activity appear completely normal, and BChE-knockout mice have been described as “lacking a phenotype” except for faster weight gain on high-fat diets. However, our recent studies with viral gene transfer of BChE in mice reveal that BChE hydrolyses the so-called “hunger hormone,” ghrelin, at a rate which strongly affects the circulating levels of this peptide hormone. This action has important consequences for weight gain and fat metabolism. Surprisingly, it also impacts emotional behaviors such as aggression. Overexpression of BChE leads to low ghrelin levels in the blood stream and reduces aggression and social stress in mice. Under certain circumstances these combined effects contribute to increased life-span in group-housed animals. These findings may generalize to humans, as recent clinical studies by multiple investigators indicate that, among patients with severe cardiovascular disease, longevity correlates with increasing levels of plasma BChE activity.

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Section: Introductionmentioning

confidence: 99%

Physiological roles for butyrylcholinesterase: A BChE-ghrelin axis

Brimijoin

Chen

Pang

et al. 2016

Chemico-Biological Interactions

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show abstract

“…Therefore, inhibition of BChE might well constitute a therapeutic target for clinical use in progressed AD when AChE inhibitors fail. Interestingly, BChE was also found to be colocalized with neurotoxic amyloid β‐plaques in the brains of AD patients and might promote amyloid β‐toxicity –. Increased levels of BChE in cortical brain regions and especially its occurrence with amyloid β‐plaques might, therefore, be a suitable marker to enable AD diagnostics.…”

Section: Introductionmentioning

confidence: 99%

A Novel Way To Radiolabel Human Butyrylcholinesterase for Positron Emission Tomography through Irreversible Transfer of the Radiolabeled Moiety

et al. 2016

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The enzyme butyrylcholinesterase (BChE) is known to be involved in the detoxification of xenobiotics in blood plasma and is associated with the progress of neurodegenerative disorders, diabetes type 2, obesity, and diseases of the cardiovascular system. In the present study, we developed carbamate-based inhibitors serving as positron emission tomography (PET) radiotracers with (18) F and (11) C as radioisotopes to visualize BChE distribution. These inhibitors are radiolabeled at the carbamate site and transfer this moiety onto BChE, which thus results in covalent and permanent radiolabeling of the enzyme. There are no comparable radiotracers for cholinesterases described to date. By ex vivo autoradiography experiments on mice brain slices and kinetic investigations, selective and covalent transfer of the radiolabeled carbamate moiety onto BChE was proven. These tracers might provide high resolution of BChE distribution in vivo to enable investigations into the pathophysiological mechanisms of diseases associated with alterations in BChE occurrence.

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“…In terms of biological viability the most notable of these haplotypes was located on chromosome 3 that overlapped with the coding region for the butyrylcholinesterase ( BCHE ) gene. BCHE has been shown to have a role in cognitive ability within humans 39 , 40 as well as rodents 41 , 42 . SNP variants close to this coding region, which overlapped with the haplotype on chromosome 3, have also been shown to be significantly associated ( P = 2.69 × 10 −8 ) with the cortical deposition of amyloid-β peptide 43 .…”

Section: Discussionmentioning

confidence: 99%

Haplotype-based association analysis of general cognitive ability in Generation Scotland, the English Longitudinal Study of Ageing, and UK Biobank

et al. 2017

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Background: Cognitive ability is a heritable trait with a polygenic architecture, for which several associated variants have been identified using genotype-based and candidate gene approaches. Haplotype-based analyses are a complementary technique that take phased genotype data into account, and potentially provide greater statistical power to detect lower frequency variants. Methods: In the present analysis, three cohort studies (n total = 48,002) were utilised: Generation Scotland: Scottish Family Health Study (GS:SFHS), the English Longitudinal Study of Ageing (ELSA), and the UK Biobank. A genome-wide haplotype-based meta-analysis of cognitive ability was performed, as well as a targeted meta-analysis of several gene coding regions. Results: None of the assessed haplotypes provided evidence of a statistically significant association with cognitive ability in either the individual cohorts or the meta-analysis. Within the meta-analysis, the haplotype with the lowest observed P-value overlapped with the D-amino acid oxidase activator ( DAOA) gene coding region. This coding region has previously been associated with bipolar disorder, schizophrenia and Alzheimer’s disease, which have all been shown to impact upon cognitive ability. Another potentially interesting region highlighted within the current genome-wide association analysis (GS:SFHS: P = 4.09 x 10 -7), was the butyrylcholinesterase ( BCHE) gene coding region. The protein encoded by BCHE has been shown to influence the progression of Alzheimer’s disease and its role in cognitive ability merits further investigation. Conclusions: Although no evidence was found for any haplotypes with a statistically significant association with cognitive ability, our results did provide further evidence that the genetic variants contributing to the variance of cognitive ability are likely to be of small effect.

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Learning performances and vulnerability to amyloid toxicity in the butyrylcholinesterase knockout mouse

Cited by 58 publications

References 53 publications

Physiological roles for butyrylcholinesterase: A BChE-ghrelin axis

Physiological roles for butyrylcholinesterase: A BChE-ghrelin axis

A Novel Way To Radiolabel Human Butyrylcholinesterase for Positron Emission Tomography through Irreversible Transfer of the Radiolabeled Moiety

Haplotype-based association analysis of general cognitive ability in Generation Scotland, the English Longitudinal Study of Ageing, and UK Biobank

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