Microglia Dystrophy Following Binge-Like Alcohol Exposure in Adolescent and Adult Male Rats.

Microglia are dynamic cells that have roles in neuronal plasticity as well as in recovery responses following neuronal injury. Although many hypothesize that hyperactivation of microglia contributes to alcohol-induced neuropathology, in other neurodegenerative conditions disruption of normal microglial processes also contributes to neuronal loss, particularly as microglia become dystrophic or dysfunctional. Based on the observation of a striking, abnormal morphology in microglia during binge-like ethanol exposure, the present study investigated the impact of excessive ethanol exposure on microglia number and dystrophic morphology in a model of alcohol dependence that includes neurodegeneration in both adult and adolescent rats.

Activation of neural stem cells from quiescence drives reactive hippocampal neurogenesis after alcohol dependence.

Neural stem cell-driven adult neurogenesis contributes to the integrity of the hippocampus. Excessive alcohol consumption in alcoholism results in hippocampal degeneration that may recover with abstinence. Reactive, increased adult neurogenesis during abstinence following alcohol dependence may contribute to recovery, but the mechanism driving reactive neurogenesis is not known.

Type 2 Neural Progenitor Cell Activation Drives Reactive Neurogenesis after Binge-Like Alcohol Exposure in Adolescent Male Rats.

Excessive alcohol consumption during adolescence remains a significant health concern as alcohol drinking during adolescence increases the likelihood of an alcohol use disorder in adulthood by fourfold. Binge drinking in adolescence is a particular problem as binge-pattern consumption is the biggest predictor of neurodegeneration from alcohol and adolescents are particularly susceptible to the damaging effects of alcohol. The adolescent hippocampus, in particular, is highly susceptible to alcohol-induced structural and functional effects, including volume and neuron loss.

Increased expression of M1 and M2 phenotypic markers in isolated microglia after four-day binge alcohol exposure in male rats.

Microglia activation and neuroinflammation are common features of neurodegenerative conditions, including alcohol use disorders (AUDs). When activated, microglia span a continuum of diverse phenotypes ranging from classically activated, pro-inflammatory (M1) microglia/macrophages to alternatively activated, growth-promoting (M2) microglia/macrophages. Identifying microglia phenotypes is critical for understanding the role of microglia in the pathogenesis of AUDs.

Alcohol Induces Parallel Changes in Hippocampal Histone H3 Phosphorylation and c-Fos Protein Expression in Male Rats.

Background: Changes in gene expression associated with alcohol-induced neuroadaptations are controlled in part by post translational histone modifications. Serine 10 phosphorylation of histone H3 (H3S10ph) has been implicated in drug-induced changes in gene expression; however, ethanol (EtOH)'s effects on H3S10ph have yet to be examined in brain. Therefore, hippocampal H3S10ph was examined after acute EtOH exposure and EtOH dependence.

Alcohol and adult hippocampal neurogenesis: promiscuous drug, wanton effects.

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.

Ectopic hippocampal neurogenesis in adolescent male rats following alcohol dependence.

The adolescent hippocampus is highly vulnerable to alcohol-induced damage, which could contribute to their increased susceptibility to alcohol use disorder. Altered adult hippocampal neurogenesis represents one potential mechanism by which alcohol (ethanol) affects hippocampal function. Based on the vulnerability of the adolescent hippocampus to alcohol-induced damage, and prior reports of long-term alcohol-induced effects on adult neurogenesis, we predicted adverse effects on adult neurogenesis in the adolescent brain following abstinence from alcohol dependence.

Microglial activation is not equivalent to neuroinflammation in alcohol-induced neurodegeneration: The importance of microglia phenotype.

Excessive alcohol intake, a defining characteristic of an alcohol use disorder (AUD), results in neurodegeneration in the hippocampus and entorhinal cortex that has been linked to a variety of cognitive deficits. Neuroinflammation is thought to be a factor in alcohol-induced neurodegeneration, and microglia activation is a key but not sole component of an inflammatory response. These experiments investigate the effects of ethanol exposure in a well-accepted model of an AUD on both microglial activation and blood brain barrier disruption (BBB) in order to understand their relationship to classical definitions of inflammation and alcohol-induced neurodegeneration.

Adolescent binge alcohol exposure alters hippocampal progenitor cell proliferation in rats: effects on cell cycle kinetics.

Binge alcohol exposure in adolescent rats potently inhibits adult hippocampal neurogenesis by altering neural progenitor cell (NPC) proliferation and survival; however, it is not clear whether alcohol results in an increase or decrease in net proliferation. Thus, the effects of alcohol on hippocampal NPC cell cycle phase distribution and kinetics were assessed in an adolescent rat model of an alcohol use disorder. Cell cycle distribution was measured using a combination of markers (Ki-67, bromodeoxyuridine incorporation, and phosphohistone H3) to determine the proportion of NPCs within G1, S, and G2/M phases of the cell cycle.

Adolescent binge alcohol exposure induces long-lasting partial activation of microglia.

Accumulating evidence indicates that the adolescent hippocampus is highly susceptible to alcohol-induced structural damage and behavioral deficits. Microglia are vitally important brain constituents needed to support and maintain proper neural function; however, alcohol's effects on microglia have only recently gained attention. The microglial response to alcohol during adolescence has yet to be studied; therefore, we examined hippocampal microglial activation in an adolescence binge alcohol exposure model.

Adolescence as a critical window for developing an alcohol use disorder: current findings in neuroscience.

Purpose Of Review: Alcohol consumption during adolescence greatly increases the likelihood that an alcohol use disorder will develop later in life. Elucidating how alcohol impacts the adolescent brain is paramount to understanding how alcohol use disorders arise. This review focuses on recent work addressing alcohol's unique effect on the adolescent brain.

Increased MMP-3 and CTGF expression during lipopolysaccharide-induced dopaminergic neurodegeneration.

Accumulating evidence indicates that neuroinflammation contributes significantly to progressive dopaminergic (DA) neurodegeneration in Parkinson's disease (PD). Altered matrix metalloproteinase-3 (MMP-3) expression has been reported in several neuroinflammatory paradigms; however, its relationship to inflammation-induced DA neurotoxicity has not been explored. To this end, we investigated the temporal expression pattern of MMP-3 and one of its downstream targets, connective tissue growth factor (CTGF), following lipopolysaccharide (LPS)-induced DA neurodegeneration.