Medicine and Health Sciences Commons^™

Sex-Specific Negative Affect-Like Behaviour And Parabrachial Nucleus Activation Induced By Bnst Stimulation In Adult Mice With Adolescent Alcohol History, Lucas Albrechet-Souza, Chelsea R. Kasten, Natalia B. Bertagna, Tiffany A. Wills

School of Medicine Faculty Publications

Adolescent alcohol use is a strong predictor for the subsequent development of alcohol use disorders later in life. Additionally, adolescence is a critical period for the onset of affective disorders, which can contribute to problematic drinking behaviours and relapse, particularly in females. Previous studies from our laboratory have shown that exposure to adolescent intermittent ethanol (AIE) vapour alters glutamatergic transmission in the bed nucleus of the stria terminalis (BNST) and, when combined with adult stress, elicits sex-specific changes in glutamatergic plasticity and negative affect-like behaviours in mice. Building on these findings, the current work investigated whether BNST stimulation could substitute …

Pro- And Anti-Inflammatory Biomarkers As Predictors Of Response To Valproate In Patients With Comorbid Alcohol Use And Bipolar Disorder-Preliminary Findings, Ilya Blokhin, Lisa Harlow, Eleonore Beurel, Feng Miao, Dana Ascherman, Claes Wahlestedt, Ihsan Salloum

Research Symposium

Objective/Hypothesis: Bipolar disorder (BD) has the highest association with alcohol and other substance use disorders compared to other major psychiatric disorders. This patient population is particularly challenging to treat. We have previously shown that some patients with co-occurring alcohol use and bipolar disorders respond to the GABAergic agonist valproate (VPA), which is known to modulates the dopaminergic system, and also as an epigenetic modifier. Predictors of therapeutic response to VPA in patients with AUD/BD are not known, and the subgroup which would benefit from VPA is still to be identified. Recent evidence suggests that AUD promotes a pro-inflammatory state while …

Alcohol As A Modifiable Risk Factor For Alzheimer’S Disease—Evidence From Experimental Studies, Devaraj V. Chandrashekar, Ross A. Steinberg, Derick Han, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive impairment and memory loss. Epidemiological evidence suggests that heavy alcohol consumption aggravates AD pathology, whereas low alcohol intake may be protective. However, these observations have been inconsistent, and because of methodological discrepancies, the findings remain controversial. Alcohol-feeding studies in AD mice support the notion that high alcohol intake promotes AD, while also hinting that low alcohol doses may be protective against AD. Chronic alcohol feeding to AD mice that delivers alcohol doses sufficient to cause liver injury largely promotes and accelerates AD pathology. The mechanisms by which alcohol can …

Adolescence, Alcohol, And Astrocytes: The Impact Of Adolescent Alcohol Use On Astrocyte-Synaptic Interactions, Structure, Function, And Behavior, Christopher Douglas Walker

Theses, Dissertations and Capstones

Alcohol is the third leading cause of preventable death in the United States and has substantial social and economic burdens. Excessive alcohol consumption in the form of binge drinking is highly prevalent among adolescents and emerging adults. Binge drinking is a form of excessive drinking, defined as consuming enough alcohol on a single occasion to result in blood alcohol concentrations above 0.08%. Approximately 55% of full-time college students aged 18- 22 years old have reported consuming alcohol in a binge manner. Furthermore, studies have shown that approximately 20% of college students meet the criteria for an alcohol use disorder (AUD). …

Effects Of Mild Traumatic Brain Injury On Ethanol Consumption And The Combined Effects On Neuroinflammation, Cognition, And Behavior In Mice, Jessica L. Hoffman

USF Tampa Graduate Theses and Dissertations

The relationship between alcohol consumption and traumatic brain injury (TBI) often focuses on alcohol consumption increasing the likelihood of incurring a TBI, rather than alcohol use outcomes after TBI. This focus is in part due to the large numbers of TBI patients visiting emergency rooms notable levels of alcohol in their blood. Additionally, increases in alcohol use disorders following TBI can be predicted by previous history of alcohol use. However, studies have also shown patients without a history of an alcohol use disorder can experience increases in problem drinking after single or multiple TBIs. Due to the diffuse impact of …

Binge Alcohol Exposure Causes Neurobehavioral Deficits And Gsk3Β Activation In The Hippocampus Of Adolescent Rats, Zhe Ji, Lin Yuan, Xiong Lu, Hanqing Ding, Jia Luo, Zun-Ji Ke

Pharmacology and Nutritional Sciences Faculty Publications

Heavy alcohol exposure causes profound damage to the adolescent brain, particularly the hippocampus, which underlie some behavioral deficits. However, the underlying molecular mechanisms remain inconclusive. The current study sought to determine whether binge alcohol exposure affects the hippocampus-related behaviors and key signaling proteins that may mediate alcohol neurotoxicity in adolescent rats. Alcohol exposure reduced the number of both NeuN-positive and doublecortin-positive cells in the hippocampus. Alcohol also induced neurodegeneration which was confirmed by ultrastructural analysis by electronic microscopy and was accompanied with the activation of microglia. Binge alcohol exposure impaired spatial learning and memory which was evaluated by the Morris …

Mechanisms And Consequences Of Epigenetic Inheritance Following Parental Preconception Alcohol Exposure, Annadorothea Asimes

Dissertations

Recent advances in genomics research have revealed that preconception behaviors and experiences of mothers and fathers, including diet, environmental toxicants, and drug abuse, can impact future offspring through epigenetic mechanisms. This means that the risky behaviors of young people, such as the extremely popular practice of binge drinking, have potentially far-reaching consequences for generations to come. While there has been considerable research into fetal alcohol exposure and parental alcoholism, there has yet to be sufficient investigation into the mechanism of epigenetic inheritance or the functional consequences of parental preconception binge pattern alcohol abuse. The hypothesis tested herein is that parental …

Intersubunit Interactions At Putative Sites Of Ethanol Action In The M3 And M4 Domains Of The Nmda Receptor Glun1 And Glun2b Subunits, Robert W. Peoples, Hong Ren, Yulin Zhao

Biomedical Sciences Faculty Research and Publications

Background and Purpose: The N-methyl-D-aspartate (NMDA) receptor is an important target of alcohol action in the brain. Recent studies in this laboratory have demonstrated that alcohol-sensitive positions in the intersubunit interfaces of the M3 and M4 domains of GluN1 and GluN2A subunits interact with respect to ethanol sensitivity and receptor kinetics, and that alcohol-sensitive positions in the M domains of GluN2A and GluN2B subunits differ. In this study we tested for interactions among alcohol-sensitive positions at the M domain intersubunit interfaces in GluN1/GluN2B NMDA receptors.

Experimental Approach: We used whole-cell patch-clamp recording in tsA201 cells expressing tryptophan substitution mutants at …

Prior Binge Ethanol Exposure Potentiates The Microglial Response In A Model Of Alcohol-Induced Neurodegeneration, Simon Alex Marshall, Chelsea Rhea Geil Nickell, Kimberly Nixon

Pharmaceutical Sciences Faculty Publications

Excessive alcohol consumption results in neurodegeneration which some hypothesize is caused by neuroinflammation. One characteristic of neuroinflammation is microglial activation, but it is now well accepted that microglial activation may be pro- or anti-inflammatory. Recent work indicates that the Majchrowicz model of alcohol-induced neurodegeneration results in anti-inflammatory microglia, while intermittent exposure models with lower doses and blood alcohol levels produce microglia with a pro-inflammatory phenotype. To determine the effect of a repeated binge alcohol exposure, rats received two cycles of the four-day Majchrowicz model. One hemisphere was then used to assess microglia via immunohistochemistry and while the other was used …

Binge Alcohol And Recovery After Traumatic Brain Injury, Ian Vaagenes

Dissertations

An estimated 275,000 Americans are hospitalized following a traumatic brain injury (TBI) every year, 80,000 of whom develop a long-term disability. The factor that places one at perhaps the greatest risk of suffering a TBI is alcohol intoxication. 30-50% of TBI sufferers have a blood alcohol level above .08 mg/dl at the time of injury, the legal limit in most U.S. states. In fact, the presence of alcohol at the time of TBI more than doubles the risk of a repeat head injury in the two years following the injury. Given the large population of TBI sufferers with alcohol intoxication …

Interactions Among Positions In The Third And Fourth Membrane-Associated Domains At The Intersubunit Interface Of The N-Methyl-D-Aspartate Receptor Forming Sites Of Alcohol Action, Hong Ren, Yulin Zhao, Donard S. Dwyer, Robert W. Peoples

Biomedical Sciences Faculty Research and Publications

The N-methyl-d-aspartate (NMDA) glutamate receptor is a major target of ethanol in the brain. Previous studies have identified positions in the third and fourth membrane-associated (M) domains of the NMDA receptor GluN1 and GluN2A subunits that influence alcohol sensitivity. The predicted structure of the NMDA receptor, based on that of the related GluA2 subunit, indicates a close apposition of the alcohol-sensitive positions in M3 and M4 between the two subunit types. We tested the hypothesis that these positions interact to regulate receptor kinetics and ethanol sensitivity by using dual substitution mutants. In single-substitution mutants, we found that a position …

Effects Of Early Alcohol Exposure On Ocular Dominance Plasticity, Crystal Lantz

Theses and Dissertations

Fetal alcohol spectrum disorder is the leading cause of mental retardation in the western world. It is associated with learning and sensory deficits. Some of these deficits are a result of faulty neuronal plasticity. Previously our lab has used ferrets to demonstrate that alcohol exposure during the third trimester of human gestation results in impaired ocular dominance plasticity (ODP). Here we have transferred this model to mice. Mice, treated with 5 mg/kg of ethanol on postnatal days 5, 7 and 9, exhibit a lack of ODP plasticity after 10 days of monocular deprivation (MD) during the critical period of visual …

Repeated Binge Pattern Ethanol Administration During Adolescence Or Adulthood: Long-Term Changes In Voluntary Ethanol Intake And Mesolimbic Dopamine Functionality In Male Rats, Antoniette Michelle Maldonado-Devincci

USF Tampa Graduate Theses and Dissertations

Binge alcohol consumption is a rising concern in the United States, especially among adolescents as during this developmental period alcohol use is usually initiated and has been shown to cause detrimental effects on brain structure and function. These findings have been established through the use of binge models in animals, where animals are repeatedly administered high doses of ethanol typically over a period of three or four days. While such work has examined the effects of a four-day and repeated three-day binge, there has been almost no work conducted aimed at investigating the long-term behavioral and neurochemical and/or functional consequences …

Molecular Requirements For Ethanol Differential Allosteric Modulation Of Ligand-Gated Ion Channels Based On Selective G Beta Gamma Modulation, Gonzalo E. Yevenes, Gustavo Moraga-Cid, Ariel Avila, Leonardo Guzman, Maximiliano Figueroa, Robert W. Peoples, Luis G. Aguayo

Biomedical Sciences Faculty Research and Publications

It is now believed that the allosteric modulation produced by ethanol in glycine receptors (GlyRs) depends on alcohol binding to discrete sites within the protein structure. Thus, the differential ethanol sensitivity of diverse GlyR isoforms and mutants was explained by the presence of specific residues in putative alcohol pockets. Here, we demonstrate that ethanol sensitivity in two LGIC members, the GlyR adult alpha1 and embryonic alpha2 subunits, can be modified through selective mutations that rescued or impaired Gbetagamma modulation. Even though that both isoforms were able to physically interact with Gbetagamma, only the alpha1 GlyR was functionally modulated by Gbetagamma …

Differential Actions Of Ethanol And Trichloroethanol At Sites In The M3 And M4 Domains Of The Nmda Receptor Glun2a (Nr2a) Subunit, Ak Salous, H Ren, Ka Lamb, Xiang-Qun Hu, Rh Lipsky, Robert W. Peoples

Biomedical Sciences Faculty Research and Publications

Background and purpose:  Alcohol produces its behavioural effects in part due to inhibition of N-methyl-d-aspartate (NMDA) receptors in the CNS. Previous studies have identified amino acid residues in membrane-associated domains 3 (M3) and 4 (M4) of the NMDA receptor that influence ethanol sensitivity. In addition, in other alcohol-sensitive ion channels, sedative-hypnotic agents have in some cases been shown to act at sites distinct from the sites of ethanol action. In this study, we compared the influence of mutations at these sites on sensitivity to ethanol and trichloroethanol, a sedative-hypnotic agent that is a structural analogue of ethanol.

Experimental approach: …