Developmental Ethanol Exposure Impacts Purkinje Cells but Not Microglia in the Young Adult Cerebellum.

Fetal alcohol spectrum disorders (FASD) caused by developmental ethanol exposure lead to cerebellar impairments, including motor problems, decreased cerebellar weight, and cell death. Alterations in the sole output of the cerebellar cortex, Purkinje cells, and central nervous system immune cells, microglia, have been reported in animal models of FASD. To determine how developmental ethanol exposure affects adult cerebellar microglia and Purkinje cells, we used a human third-trimester binge exposure model in which mice received ethanol or saline from postnatal (P) days 4-9.

Ethanol Induces Neuroinflammation in a Chronic Plus Binge Mouse Model of Alcohol Use Disorder via TLR4 and MyD88-Dependent Signaling.

Ethanol induces neuroinflammation, which is believed to contribute to the pathogenesis of alcohol use disorder (AUD). Toll-like receptors (TLRs) are a group of pattern recognition receptors (PRRs) expressed on both immune cells, including microglia and astrocytes, and non-immune cells in the central nervous system (CNS). Studies have shown that alcohol activates TLR4 signaling, resulting in the induction of pro-inflammatory cytokines and chemokines in the CNS.

Developmental ethanol exposure has minimal impact on cerebellar microglial dynamics, morphology, and interactions with Purkinje cells during adolescence.

Introduction: Fetal alcohol spectrum disorders (FASD) are the most common cause of non-heritable, preventable mental disability, occurring in almost 5% of births in the United States. FASD lead to physical, behavioral, and cognitive impairments, including deficits related to the cerebellum. There is no known cure for FASD and their mechanisms remain poorly understood.

Ethanol-induced cerebellar transcriptomic changes in a postnatal model of fetal alcohol spectrum disorders: Focus on disease onset.

Fetal alcohol spectrum disorders (FASD) are a group of neurodevelopmental disorders caused by ethanol exposure , which can result in neurocognitive and behavioral impairments, growth defects, and craniofacial anomalies. FASD affects up to 1-5% of school-aged children in the United States, and there is currently no cure. The underlying mechanisms involved in ethanol teratogenesis remain elusive and need greater understanding to develop and implement effective therapies.

Cerebellar Transcriptomic Analysis in a Chronic plus Binge Mouse Model of Alcohol Use Disorder Demonstrates Ethanol-Induced Neuroinflammation and Altered Glial Gene Expression.

Alcohol use disorder (AUD) is one of the most common preventable mental health disorders and can result in pathology within the CNS, including the cerebellum. Cerebellar alcohol exposure during adulthood has been associated with disruptions in proper cerebellar function. However, the mechanisms regulating ethanol-induced cerebellar neuropathology are not well understood.

Effects of chronic and binge ethanol administration on mouse cerebellar and hippocampal neuroinflammation.

Hippocampal and cerebellar neuropathology occurs in individuals with alcohol use disorders (AUD), resulting in impaired cognitive and motor function. Evaluate the effects of ethanol on the expression of pro- and anti-inflammatory molecules, as well as the effects of the anti-inflammatory PPAR-γ agonist pioglitazone in suppressing ethanol-induced neuroinflammation. Adult male and female mice were treated chronically with ethanol for just under a month followed by a single acute binge dose of ethanol.

Neuroimaging predictors of longitudinal disability and cognition outcomes in multiple sclerosis patients: A systematic review and meta-analysis.

Background: Cross-sectional magnetic resonance imaging (MRI) studies have generated substantial evidence relating neuroimaging abnormalities to clinical and cognitive decline in multiple sclerosis (MS). Longitudinal neuroimaging studies may have additional value for predicting future cognitive deficits or clinical impairment, potentially leading to earlier interventions and better disease management. We conducted a meta-analysis of longitudinal studies using neuroimaging to predict cognitive decline (i.

Ethanol effects on cerebellar myelination in a postnatal mouse model of fetal alcohol spectrum disorders.

Fetal alcohol spectrum disorders (FASD) are alarmingly common, result in significant personal and societal loss, and there are no effective treatments for these disorders. Cerebellar neuropathology is common in FASD and can cause impaired cognitive and motor function. The current study evaluates the effects of ethanol on oligodendrocyte-lineage cells, as well as molecules that modulate oligodendrocyte differentiation and function in the cerebellum in a postnatal mouse model of FASD.

Ethanol modulation of hippocampal neuroinflammation, myelination, and neurodevelopment in a postnatal mouse model of fetal alcohol spectrum disorders.

Fetal alcohol spectrum disorders (FASD) are alarmingly common and result in significant personal and societal loss. Neuropathology of the hippocampus is common in FASD leading to aberrant cognitive function. In the current study, we evaluated the effects of ethanol on the expression of a targeted set of molecules involved in neuroinflammation, myelination, neurotransmission, and neuron function in the developing hippocampus in a postnatal model of FASD.

Divergent and overlapping hippocampal and cerebellar transcriptome responses following developmental ethanol exposure during the secondary neurogenic period.

Background: The developing hippocampus and cerebellum, unique among brain regions, exhibit a secondary surge in neurogenesis during the third trimester of pregnancy. Ethanol (EtOH) exposure during this period is results in a loss of tissue volume and associated neurobehavioral deficits. However, mechanisms that link EtOH exposure to teratology in these regions are not well understood.

Microglia and astrocytes show limited, acute alterations in morphology and protein expression following a single developmental alcohol exposure.

Fetal alcohol spectrum disorders (FASD) are the most common cause of nonheritable, preventable mental disability and are characterized by cognitive, behavioral, and physical impairments. FASD occurs in almost 5% of births in the United States, but despite this prevalence there is no known cure, largely because the biological mechanisms that translate alcohol exposure to neuropathology are not well understood. While the effects of early ethanol exposure on neuronal survival and circuitry have received more attention, glia, the cells most closely tied to initiating and propagating inflammatory events, could be an important target for alcohol in the developing brain.

Ethanol modulation of cerebellar neuroinflammation in a postnatal mouse model of fetal alcohol spectrum disorders.

Fetal alcohol spectrum disorders (FASD) are alarmingly common, result in significant personal and societal loss, and there is no effective treatment for these disorders. Cerebellar neuropathology is common in FASD and causes aberrant cognitive and motor function. Ethanol-induced neuroinflammation is believed to contribute to neuropathological sequelae of FASD, and was previously demonstrated in the cerebellum in animal models of FASD.

Neuroinflammatory contribution of microglia and astrocytes in fetal alcohol spectrum disorders.

Ethanol exposure to the fetus during pregnancy can result in fetal alcohol spectrum disorders (FASD). These disorders vary in severity, can affect multiple organ systems, and can lead to lifelong disabilities. Damage to the central nervous system (CNS) is common in FASD, and can result in altered behavior and cognition.

The RNA-binding protein HuR contributes to neuroinflammation by promoting C-C chemokine receptor 6 (CCR6) expression on Th17 cells.

In both multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), the C-C chemokine receptor 6 (CCR6) is critical for pathogenic T helper 17 (Th17) cell migration to the central nervous system (CNS). Whereas many cytokines and their receptors are potently regulated via post-transcriptional mechanisms in response to various stimuli, how CCR6 expression is post-transcriptionally regulated in Th17 cells is unknown. Here, using RNA-binding protein HuR conditional knock-out (KO) and wild-type (WT) mice, we present evidence that HuR post-transcriptionally regulates CCR6 expression by binding to and stabilizing mRNA and by promoting CCR6 translation.

Peroxisome Proliferator-Activated Receptor-γ Agonists: Potential Therapeutics for Neuropathology Associated with Fetal Alcohol Spectrum Disorders.

Fetal alcohol spectrum disorders (FASD) result from fetal exposure to alcohol during pregnancy. These disorders present a variety of sequelae including involvement of the central nervous system (CNS) with lasting impact on cognitive function and behavior. FASD occur at an alarming rate and have significant personal and societal impact.

Protection against alcohol-induced neuronal and cognitive damage by the PPARγ receptor agonist pioglitazone.

Binge alcohol drinking has emerged as a typical phenomenon in young people. This pattern of drinking, repeatedly leading to extremely high blood and brain alcohol levels and intoxication is associated with severe risks of neurodegeneration and cognitive damage. Mechanisms involved in excitotoxicity and neuroinflammation are pivotal elements in alcohol-induced neurotoxicity.

Inflammatory responses to alcohol in the CNS: nuclear receptors as potential therapeutics for alcohol-induced neuropathologies.

Fetal alcohol spectrum disorder (FASD), which results from ethanol exposure during pregnancy, and alcohol use disorder (AUD), which includes both binge and chronic alcohol abuse, are strikingly common and costly at personal and societal levels. These disorders are associated with significant pathology, including that observed in the CNS. It is now appreciated in both humans and animal models that ethanol can induce inflammation in the CNS.

Pioglitazone blocks ethanol induction of microglial activation and immune responses in the hippocampus, cerebellum, and cerebral cortex in a mouse model of fetal alcohol spectrum disorders.

Background: Fetal alcohol spectrum disorders (FASD) result from fetal exposure to alcohol and are the leading cause of mental retardation in the United States. There is currently no effective treatment that targets the causes of these disorders. Thus, novel therapies are critically needed to limit the neurodevelopmental and neurodegenerative pathologies associated with FASD.

Fetal alcohol spectrum disorders and neuroimmune changes.

The behavioral consequences of fetal alcohol spectrum disorders (FASD) are serious and persist throughout life. The causative mechanisms underlying FASD are poorly understood. However, much has been learned about FASD from human structural and functional studies as well as from animal models, which have provided a greater understanding of the mechanisms underlying FASD.

The immunomodulator AS101 suppresses production of inflammatory cytokines and ameliorates the pathogenesis of experimental autoimmune encephalomyelitis.

We reported that AS101 (organotellurium compound, trichloro(dioxoethylene-O,O') tellurate) inhibited the differentiation of Th17 cells and reduced the production of IL-17 and GM-CSF. In addition, AS101 promoted the production of IL-2 in activated T cells. Flow cytometric analysis showed that AS101 inhibited Th17 cell proliferation.

Effects of ethanol on immune response in the brain: region-specific changes in adolescent versus adult mice.

Background: Alcohol use occurs across the life span beginning in adolescence and continuing through adulthood. Ethanol (EtOH)-induced pathology varies with age and includes changes in neurogenesis, neurodegeneration, and glial cell activation. EtOH-induced changes in glial activation and immune activity are believed to contribute to EtOH-induced neuropathology.

Effects of ethanol on immune response in the brain: region-specific changes in aged mice.

Background: Alcohol abuse has dramatic effects on the health of the elderly. Recent studies indicate that ethanol increases immune activity in younger animals and that some of these proinflammatory molecules alter alcohol consumption and addiction. However, the effects of alcohol on immune activation in aged animals have not been thoroughly investigated.

β-Lapachone ameliorization of experimental autoimmune encephalomyelitis.

β-Lapachone is a naturally occurring quinine, originally isolated from the bark of the lapacho tree (Tabebuia avellanedae) which is currently being evaluated in clinical trials for the treatment of cancer. In addition, recent investigations suggest its potential application for treatment of inflammatory diseases. Multiple sclerosis (MS) is an autoimmune disorder characterized by CNS inflammation and demyelination.