Alcohol and Neurodegeneration

Crews, Fulton T.

doi:10.1111/j.1527-3458.1999.tb00112.x

Cited by 51 publications

(39 citation statements)

References 93 publications

(94 reference statements)

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“…In neuroimaging studies, it is well documented that the duration of alcoholism is inversely related to the volume of some cerebral regions (Crews, 1999;Harper and Matsumoto, 2005;Laakso et al, 2002). Volumes of the dlPFC and the ORB are inversely correlated to the duration of alcoholism.…”

Section: Discussionmentioning

confidence: 97%

Reduced Glial and Neuronal Packing Density in the Orbitofrontal Cortex in Alcohol Dependence and Its Relationship with Suicide and Duration of Alcohol Dependence

Miguel-Hidalgo

Overholser

Meltzer

et al. 2006

Alcoholism Clin & Exp Res

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Section: Discussionmentioning

confidence: 97%

Reduced Glial and Neuronal Packing Density in the Orbitofrontal Cortex in Alcohol Dependence and Its Relationship with Suicide and Duration of Alcohol Dependence

Miguel-Hidalgo

Overholser

Meltzer

et al. 2006

Alcoholism Clin & Exp Res

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“…Although there are many theories about the development of AUDs, all involve the fact that repeated bouts of excessive alcohol intake change the brain in a way that drives a loss of control over consumption (Koob and Le Moal, 1997). This loss of control may be driven by hijacked learning processes, impairments in behavioral control, and/or impaired decision-making (Crews, 1999; Noel et al, 2013). All of these processes involve, at least partially, the contribution of an intact hippocampus, and a wide variety of studies have shown that excessive alcohol intake impacts the structure and function of hippocampal circuitry.…”

Section: Introductionmentioning

confidence: 99%

“…Excessive alcohol consumption has widespread deleterious effects on many of these organ systems, but central nervous system injury is a critical consequence as 50 to 75% of alcohol-dependent adults show permanent cognitive impairment (Eckardt and Martin, 1986). These impairments are thought to be due to both structural and functional changes resulting from excessive alcohol consumption (Crews, 1999; Sullivan and Pfefferbaum, 2005). Alcohol appears to target some brain regions more than others with a critical cluster of alcohol-induced impairments in behavioral control, learning, memory, mood, and decision-making attributed, at least in part, to the integrity of the hippocampus (Mechtcheriakov et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Alcohol and adult hippocampal neurogenesis: Promiscuous drug, wanton effects

Geil

Hayes

McClain

et al. 2014

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Adult neurogenesis is now widely accepted as an important contributor to hippocampal integrity and function but also dysfunction when adult neurogenesis is affected in neuropsychiatric diseases such as alcohol use disorders. Excessive alcohol consumption, the defining characteristic of alcohol use disorders, results in a variety of cognitive and behavioral impairments related wholly or in part to hippocampal structure and function. Recent preclinical work has shown that adult neurogenesis may be one route by which alcohol produces hippocampal neuropathology. Alcohol is a pharmacologically promiscuous drug capable of interfering with adult neurogenesis through multiple mechanisms. This review will discuss the primary mechanisms underlying alcohol-induced changes in adult hippocampal neurogenesis including alcohol's effects on neurotransmitters, CREB and its downstream effectors, and the neurogenic niche.

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“…Neuroprotective agents are hypothesized to have high therapeutic utility for the treatment of AUDs (Crews, 1999). Excessive alcohol intake, characteristic of AUDs, results in neurodegeneration and cognitive and behavioral impairment, effects which are hypothesized to influence the transition to addiction (Koob and Le Moal, 1997; Crews, 1999; Sullivan and Pfefferbaum, 2005).…”

Section: Introductionmentioning

confidence: 99%

Transdermal delivery of cannabidiol attenuates binge alcohol-induced neurodegeneration in a rodent model of an alcohol use disorder

Liput

Hammell²,

Stinchcomb

et al. 2013

Pharmacology Biochemistry and Behavior

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Excessive alcohol consumption, characteristic of alcohol use disorders, results in neurodegeneration and behavioral and cognitive impairments that are hypothesized to contribute to the chronic and relapsing nature of alcoholism. Therefore, the current study aimed to advance the preclinical development of transdermal delivery of cannabidiol (CBD) for the treatment of alcohol-induced neurodegeneration. In experiment 1, 1.0%, 2.5% and 5.0% CBD gels were evaluated for neuroprotection. The 5.0% CBD gel resulted in a 48.8% reduction in neurodegeneration in the entorhinal cortex assessed by Fluoro-Jade B (FJB), which trended to statistical significance (p = 0.069). Treatment with the 5.0% CBD gel resulted in day 3 CBD plasma concentrations of ~100.0 ng/mL so this level was used as a target concentration for development of an optimized gel formulation. Experiment 2 tested a next generation 2.5% CBD gel formulation, which was compared to CBD administration by intraperitoneal injection (IP; 40.0 mg/kg/d). This experiment found similar magnitudes of neuroprotection following both routes of administration; transdermal CBD decreased FJB+ cells in the entorhinal cortex by 56.1% (p < 0.05), while IP CBD resulted in a 50.6% (p < 0.05) reduction in FJB+ cells. These results demonstrate the feasibility of using CBD transdermal delivery systems for the treatment of alcohol-induced neurodegeneration.

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Alcohol and Neurodegeneration

Cited by 51 publications

References 93 publications

Reduced Glial and Neuronal Packing Density in the Orbitofrontal Cortex in Alcohol Dependence and Its Relationship with Suicide and Duration of Alcohol Dependence

Reduced Glial and Neuronal Packing Density in the Orbitofrontal Cortex in Alcohol Dependence and Its Relationship with Suicide and Duration of Alcohol Dependence

Alcohol and adult hippocampal neurogenesis: Promiscuous drug, wanton effects

Transdermal delivery of cannabidiol attenuates binge alcohol-induced neurodegeneration in a rodent model of an alcohol use disorder

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