Upregulation of β‐Catenin Levels in Superior Frontal Cortex of Chronic Alcoholics

Alhousseini, Ali; Sivanandam, Thamil Mani; Bradbury, E. L.; Tannenberg, R. K.; Dodd, Peter R.; Gu, Qiang

doi:10.1111/j.1530-0277.2008.00670.x

Cited by 14 publications

(15 citation statements)

References 102 publications

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“…This may be secondary due to the commensurate loss of BMP activity, although acute ethanol can also rapidly deplete nuclear β-catenin from osteoblasts (Chen et al 2010), a finding consistent with our own studies with neural crest progenitors. For neurons the findings are contradictory, with chronic ethanol exposure reducing the total β-catenin content of cultured hippocampal neurons (Singh et al 2009) but elevating β-catenin in the frontal cortex of chronic alcoholics (Al-Housseini et al 2008). These neuronal studies did not distinguish between the cytoskeletal and nuclear pools and thus the functional consequences of those changes are uncertain.…”

Section: Discussionmentioning

confidence: 99%

Calcium-mediated repression of β-catenin and its transcriptional signaling mediates neural crest cell death in an avian model of fetal alcohol syndrome

Flentke

Garic

Amberger

et al. 2011

Birth Defects Research Part A: Clinical and Molecular Teratolog

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Fetal Alcohol Syndrome (FAS) is a common birth defect in many societies. Affected individuals have neurodevelopmental disabilities and a distinctive craniofacial dysmorphology. These latter deficits originate during early development from the ethanol-mediated apoptotic depletion of cranial facial progenitors, a population known as the neural crest. We showed previously that this apoptosis is caused because acute ethanol exposure activates a G protein-dependent intracellular calcium within cranial neural crest progenitors, and this calcium transient initiates the cell death. The dysregulated signals that reside downstream of ethanol’s calcium transient and effect neural crest death are unknown. Here we show that ethanol’s repression of the transcriptional effector β-catenin causes the neural crest losses. Clinically-relevant ethanol concentrations (22–78 mM) rapidly deplete nuclear β-catenin from neural crest progenitors, with accompanying losses of β-catenin transcriptional activity and downstream genes that govern neural crest induction, expansion and survival. Using forced expression studies we show that β-catenin loss of function (via dominant-negative TCF) recapitulates ethanol’s effects on neural crest apoptosis, whereas β-catenin gain-of-function in ethanol’s presence preserves neural crest survival. Blockade of ethanol’s calcium transient using Bapta-AM normalizes β-catenin activity and prevents the neural crest losses, whereas ionomycin treatment is sufficient to destabilize β-catenin. We propose that ethanol’s repression of β-catenin causes the neural crest losses in this model of FAS. β-Catenin is a novel target for ethanol’s teratogenicity. β-Catenin/Wnt signals participate in many developmental events and its rapid and persistent dysregulation by ethanol may explain why the latter is such a potent teratogen.

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Section: Discussionmentioning

confidence: 99%

Calcium-mediated repression of β-catenin and its transcriptional signaling mediates neural crest cell death in an avian model of fetal alcohol syndrome

Flentke

Garic

Amberger

et al. 2011

Birth Defects Research Part A: Clinical and Molecular Teratolog

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“…Increased levels of β-catenin have been reported in a wide variety of neurological disorders, including AD (14,15), HD (13), and alcoholism (40), but the contribution of β-catenin to these disorders remains unclear. In HD, β-catenin levels are significantly increased in the brains of HD patients as well as in mouse and Drosophila models of HD, and targeted reduction of β-catenin was shown to have a therapeutic effects (13).…”

Section: Discussionmentioning

confidence: 99%

Cognitive flexibility and long-term depression (LTD) are impaired following β-catenin stabilization in vivo

Mills¹,

Bartlett²,

Dissing-Olesen

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Complex learning and memory are believed to require the weakening or elimination of synapses in the brain, a process mediated by adhesion molecules, which maintain synapse strength and stability. In the present study, we examine in vivo the effects of stabilization of β-catenin, an intracellular protein that is a component of the cadherin adhesion complex. We find that stabilization of β-catenin in the brain prevents normal activity-dependent downscaling of synapse strength, resulting in a striking impairment in cognitive flexibility. These results demonstrate that β-catenin plays an important role in learning and memory and that aberrant increases in synaptic adhesion can have detrimental effects on cognitive function.

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“…Both casein-kinase 1 episolon and delta (CK1 ε and CK1 δ , respectively) are additional circadian genes tied to alcoholism and alcohol relapse (Al-Housseini et al, 2008; Perreau-Lenz et al, 2012). We will refer to both isoforms as CK1 ε / δ because most studies do not distinguish between the two.…”

Section: Circadian Gene Mutations and Alcohol Seeking And Rewardmentioning

confidence: 99%

Circadian rhythms and addiction: Mechanistic insights and future directions.

Logan

Williams

McClung

2014

Behavioral Neuroscience

119

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Circadian rhythms are prominent in many physiological and behavioral functions. Circadian disruptions either by environmental or molecular perturbation can have profound health consequences, including the development and progression of addiction. Both animal and humans studies indicate extensive bidirectional relationships between the circadian system and drugs of abuse. Addicted individuals display disrupted rhythms, and chronic disruption or particular chronotypes, may increase the risk for substance abuse and relapse. Moreover, polymorphisms in circadian genes and an evening chronotype have been linked to mood and addiction disorders, and recent efforts suggest an association with the function of reward neurocircuitry. Animal studies are beginning to determine how altered circadian gene function results in drug induced neuroplasticity and behaviors. Many studies suggest a critical role for circadian rhythms in reward-related pathways in the brain and indicate that drugs of abuse directly affect the central circadian pacemaker. In this review, we highlight key findings demonstrating the importance of circadian rhythms in addiction, and how future studies will reveal important mechanistic insights into the involvement of circadian rhythms in drug addiction.

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Upregulation of β‐Catenin Levels in Superior Frontal Cortex of Chronic Alcoholics

Cited by 14 publications

References 102 publications

Calcium-mediated repression of β-catenin and its transcriptional signaling mediates neural crest cell death in an avian model of fetal alcohol syndrome

Calcium-mediated repression of β-catenin and its transcriptional signaling mediates neural crest cell death in an avian model of fetal alcohol syndrome

Cognitive flexibility and long-term depression (LTD) are impaired following β-catenin stabilization in vivo

Circadian rhythms and addiction: Mechanistic insights and future directions.

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