Medicine and Health Sciences Commons^™

Functional Activation Of Newborn Neurons Following Alcohol-Induced Reactive Neurogenesis, Natalie N. Nawarawong, Chelsea G. Nickell, Deann M. Hopkins, James R. Pauly, Kimberly Nixon

Pharmaceutical Sciences Faculty Publications

Abstinence after alcohol dependence leads to structural and functional recovery in many regions of the brain, especially the hippocampus. Significant increases in neural stem cell (NSC) proliferation and subsequent “reactive neurogenesis” coincides with structural recovery in hippocampal dentate gyrus (DG). However, whether these reactively born neurons are integrated appropriately into neural circuits remains unknown. Therefore, adult male rats were exposed to a binge model of alcohol dependence. On day 7 of abstinence, the peak of reactive NSC proliferation, rats were injected with bromodeoxyuridine (BrdU) to label dividing cells. After six weeks, rats underwent Morris Water Maze (MWM) training then were …

Removal Of Mimosine From Leucaena Leucocephala (Lam.) De Wit Seeds To Increase Their Benefits As Nutraceuticals, Sri Wardatun, Yahdiana Harahap, Abdul Mun'im, Fadlina Chany Saputri Dr., Noorwati Sutandyo

Pharmaceutical Sciences and Research

The Leucaena leucocephala (Lam.) de Wit tree contains pharmacologically active compounds and can easily be found in abundant quantities. The utilization of this tree as a source of nutraceuticals would increase its value. The extraction yields show the number of compounds that have been extracted by solvent. However, Leucaena leucocephala (Lam.) de Wit seeds also contain mimosine, which can cause hair loss. The present study investigated the process of removing mimosine from the seeds. Three treatments were applied to these seeds: treatment without soaking, soaking with distilled water for 24 hours, and splitting the seeds in half and then soaking …

Recovery Of Hippocampal-Dependent Learning Despite Blunting Reactive Adult Neurogenesis After Alcohol Dependence, Chelsea G. Nickell, K. Ryan Thompson, James R. Pauly, Kimberly Nixon

Pharmaceutical Sciences Faculty Publications

Background:

The excessive alcohol drinking that occurs in alcohol use disorder (AUD) causes neurodegeneration in regions such as the hippocampus, though recovery may occur after a period of abstinence. Mechanisms of recovery are not clear, though reactive neurogenesis has been observed in the hippocampal dentate gyrus following alcohol dependence and correlates to recovery of granule cell number.

Objective:

We investigated the role of neurons born during reactive neurogenesis in the recovery of hippocampal learning behavior after 4-day binge alcohol exposure, a model of an AUD. We hypothesized that reducing reactive neurogenesis would impair functional recovery.

Methods:

Adult male rats were …

Type 2 Neural Progenitor Cell Activation Drives Reactive Neurogenesis After Binge-Like Alcohol Exposure In Adolescent Male Rats, Chelsea Rhea Geil Nickell, Hui Peng, Dayna M. Hayes, Kevin Y. Chen, Justin A. Mcclain, Kimberly Nixon

Pharmaceutical Sciences Faculty Publications

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. However, hippocampal structure and function may recover with abstinence and, like in adults, a reactive burst in hippocampal neurogenesis in abstinence may contribute to …

Binge Alcohol Exposure Transiently Changes The Endocannabinoid System: A Potential Target To Prevent Alcohol-Induced Neurodegeneration, Daniel J. Liput, James R. Pauly, Audra L. Stinchcomb, Kimberly Nixon

Pharmaceutical Sciences Faculty Publications

Excessive alcohol consumption leads to neurodegeneration, which contributes to cognitive decline that is associated with alcohol use disorders (AUDs). The endocannabinoid system has been implicated in the development of AUDs, but little is known about how the neurotoxic effects of alcohol impact the endocannabinoid system. Therefore, the current study investigated the effects of neurotoxic, binge-like alcohol exposure on components of the endocannabinoid system and related N-acylethanolamines (NAEs), and then evaluated the efficacy of fatty acid amide hydrolase (FAAH) inhibition on attenuating alcohol-induced neurodegeneration. Male rats were administered alcohol according to a binge model, which resulted in a transient decrease in …

Increased Expression Of M1 And M2 Phenotypic Markers In Isolated Microglia After Four-Day Binge Alcohol Exposure In Male Rats, Hui Peng, Chelsea Rhea Geil Nickell, Kevin Y. Chen, Justin A. Mcclain, Kimberly Nixon

Pharmaceutical Sciences Faculty Publications

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. Therefore, male rats were gavaged with 25% (w/v) ethanol or isocaloric control diet every 8 h for 4 days and sacrificed at 0, 2, 4, and 7 days after alcohol exposure (e.g., T0, T2, etc.). Microglia were isolated from hippocampus and entorhinal cortices by Percoll density gradient …

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 …

Assessing The Relationship Between The Blood-Air Partition Coefficient And Fractional Uptake Of Inspired Halothane, Acetone, And Ethanol Vapors In The Airways Of The C57bl/6j Mouse, Joshua Baruch Baldino

Honors Scholar Theses

The following series of studies investigates the elimination and uptake trends of halothane, acetone, and ethanol vapors in the airways of C57BL/6J mice. These vapors were chosen because they span a wide range of solubilities, as indicated by their blood-air partition coefficients, and are not associated with any significant airway metabolism or reactivity with tissue substrates in vivo. Mice were exposed to a homogeneous vapor mixture containing a 1:1:1 ratio of halothane, acetone, and ethanol at relative concentrations of approximately 10 ppm. Exposure studies were performed with mice in two states, conscious and deceased, in order to provide control …

Role Of Ethanol As A Cofactor In Haart Induced Hepatic Steatosis And Injury., Hridgandh Donde

Electronic Theses and Dissertations

Highly Active Antiretroviral Therapy (HAART) has led to a significant increase in the life expectancy of HIV patients; however, there are significant side effects including lipodystrophy and hepatotoxicity. Alcohol abuse is highly prevalent in HIV infected individuals and hence may be a significant negative cofactor in HAART induced hepatotoxicity. The present study examines the mechanisms underlying HAART and alcohol induced hepatotoxicity. The effects of HAART drugs (azidothymidine, and Indinavir sulphate) in combination with alcohol were examined in in vivo animal model. Alcohol and HAART drug interactions and hepatotoxicity were also assessed in-vivo using an animal model of chronic alcohol feeding. …

Interspecies Pharmacokinetic Scaling And Metabolism Of Alcohols And Glycols, Pankaj Gupta

Theses and Dissertations

Background: Despite the numerous pharmaceutical applications of alcohols andglycols, the interspecies differences with respect to their pharmacokinetics (PK) arepoorly understood. The aim of this research was to use in-vivo and in-vitro approaches to compare and model the PK characteristics across various species.Methods: Appropriate published in-vivo studies (in different species) foralcohols and glycols were carefully selected. PK analysis was performed using (a) noncompartmental analysis and (b) compartmental modeling to estimate relevant dose-independent PK parameters. Next, six alcohols (methanol, ethanol, 1 -propanol, 1 -butanol, 1-hexanol, and 1-octanol), two glycols (ethylene glycol and propylene glycol)and one secondary alcohol (2-propanol) were examined as in-vitro …