Medicine and Health Sciences Commons^™

Methamphetamine-Induced Dna Double-Stranded Breaks: The Impact Of The Dopamine Transporter And Insights Into The Mechanisms Of Dna Damage In Mouse Neuro 2a Cells, Lizette Couto

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) abuse remains a global health concern, with emerging evidence highlighting its genotoxic potential. In the central nervous system METH enters dopaminergic cells primarily through the dopamine transporter (DAT), which controls the dynamics of dopamine (DA) neurotransmission by driving the reuptake of extracellular DA into the presynaptic neuronal cell. Additional effects of METH on the storage of DA in synaptic vesicles lead to the dysregulated cytosolic accumulation of DA. Previous studies have shown that after METH disrupts intracellular vesicular stores of DA, the excess DA in the cytosol is rapidly oxidized. This generates an abundance of reactive oxygen species …

Prenatal Exposure To Methamphetamine Causes Vascular Dysfunction In Adult Male Offspring, Hasitha Chavva, Adam M. Belcher, Daniel A. Brazeau, Boyd Rorabaugh

Pharmaceutical Science and Research

Methamphetamine use during pregnancy can have negative consequences on the offspring. However, most studies investigating the impact of prenatal exposure to methamphetamine have focused on behavioral and neurological outcomes. Relatively little is known regarding the impact of prenatal methamphetamine on the adult cardiovascular system. This study investigated the impact of chronic fetal exposure to methamphetamine on vascular function in adult offspring. Pregnant female rats received daily saline or methamphetamine (5 mg/kg) injections starting on gestational day 1 and continuing until the pups were born. Vascular function was assessed in 5 month old offspring. Prenatal methamphetamine significantly decreased both the efficacy …

Investigation Of Postmortem Methamphetamine Cases Submitted To The New York City Office Of Chief Medical Examiner, Isaiah Jewell

Student Theses

Methamphetamine (N-methylamphetamine) is a central nervous system stimulant (CNS) and sympathomimetic drug with a high addiction potential. In the United States, there has been a significant increase in the presence of methamphetamine in recent years, specifically in the Northeastern region of the country. The New York City Office of Chief Medical Examiner (NYC-OCME) postmortem methamphetamine casework from 2018 and 2019 was analyzed and revealed that the presence of the drug increased drastically within a span of one year, jumping from 65 cases in 2018 to 99 cases in 2019. Males were overwhelmingly responsible for much of the casework, taking up …

Methamphetamine-Induced Changes In Myocardial Gene Transcription Are Sex-Dependent, Hasitha Chavva, Daniel A. Brazeau, James Denvir, Donald A. Primerano, Jun Fan, Sarah L. Seeley, Boyd R. Rorabaugh

Pharmaceutical Science and Research

Background: Prior work demonstrated that female rats (but not their male littermates) exposed to methamphetamine become hypersensitive to myocardial ischemic injury. Importantly, this sex-dependent effect persists following 30 days of subsequent abstinence from the drug, suggesting that it may be mediated by long term changes in gene expression that are not rapidly reversed following discontinuation of methamphetamine use. The goal of the present study was to determine whether methamphetamine induces sex-dependent changes in myocardial gene expression and whether these changes persist following subsequent abstinence from methamphetamine.

Results: Methamphetamine induced changes in the myocardial transcriptome were significantly greater in female hearts …

Intravenous Prenatal Nicotine Exposure Alters Meth-Induced Hyperactivity, Conditioned Hyperactivity, And Bdnf In Adult Rat Offspring, Ryan T. Lacy, Russell. W. Brown, Amanda J. Morgan, Charles F. Mactutus, Steven B. Harrod

Russell W. Brown

In the USA, approximately 15% of women smoke tobacco cigarettes during pregnancy. In utero tobacco smoke exposure produces somatic growth deficits like intrauterine growth restriction and low birth we

Intravenous Prenatal Nicotine Exposure Alters Meth-Induced Hyperactivity, Conditioned Hyperactivity, And Bdnf In Adult Rat Offspring, Ryan T. Lacy, Russell. W. Brown, Amanda J. Morgan, Charles F. Mactutus, Steven B. Harrod

ETSU Faculty Works

In the USA, approximately 15% of women smoke tobacco cigarettes during pregnancy. In utero tobacco smoke exposure produces somatic growth deficits like intrauterine growth restriction and low birth we

Temporal And Spatial Changes In The Pattern Of Iba1 And Cd68 Staining In The Rat Brain Following Severe Traumatic Brain Injury, Debbie Smith, Diane Brooks, Eric Wohlgehagen, Thomas Rau, David Poulsen

Biomedical and Pharmaceutical Sciences Faculty Publications

We have previously demonstrated that acute treatment with low dose methamphetamine is neuroprotectivein a rat model of severe traumatic brain injury (TBI). Using gene expression analysis, we further showed that methamphetamine treatment significantly reduced the expression of proinflammatory genes after severe TBI. Therefore, to further investigate the potential effects of methamphetamine treatment on the neuroinflammatory response, we examined immunofluorescent staining of Iba1 and CD68, two marker of neuroinflammation, in the rat lateral fluid percussion injury model of severe TBI. In this study, we observed temporal and spatial alterations in the pattern of Iba1 and CD68 labeling within two weeks after …

Glial Cell Modulators And Associated Anti-Inflammatory Activity: Implications In Reducing Methamphetamine Abuse-Related Behaviors In Rodents, Sarah Snider

Theses and Dissertations

Methamphetamine is a psychomotor stimulant that produces hyperactivity and euphoria and can lead to drug-seeking and abuse. An estimate from 2005 put the cost of methamphetamine abuse to society at an estimated 23.4 billion dollars. One of methamphetamine's effects is activation of glial cells and associated neuroinflammatory activity in the periphery and CNS. Glia are responsible for maintaining calcium homeostasis, neuroplasticity, immune activity, and cell signaling. Activation of glia and neuroinflammation are becoming recognized as links in drug abuse-related behavior. The goal of the present work was to assess the ability of ibudilast, AV1013, and minocycline, three glial cell modulating …

Regulation Of Alpha Synuclein Following Chronic Methamphetamine Administration In Guinea Pigs: Correlation With Memory And Synaptic Plasticity, Adnouse Blanc

PCOM Biomedical Studies Student Scholarship

Methamphetamine (METH) is a highly addictive drug of abuse that has a severe impact on neuronal changes in the brain including modulations of plasticity, cognitive dysfunction, as well as memory impairment. These changes can be seen as modifications in the expression of biochemical markers associated with synaptic plasticity. One such marker associated with memory impairment is alpha synuclein (α-syn). Alteration of α-syn expression has been linked to memory impairment in patients with Alzheimer’s disease (AD) and Parkinson’s disease (PD). Here we assess the effect of chronic METH treatment in correlation to cognitive functions.

Twenty-nine guinea pigs (male, 150-250 g) were …

The Mesocorticolimbic Dopamine Pathway Reconstituted In Vitro: Glutamate Receptors And Corticosteroid-Methamphetamine Neurotoxicity, Jennifer N. Berry

Theses and Dissertations--Psychology

Stress promotes the use of methamphetamine and other recreational substances and is often implicated in relapse to stimulant use. Thus, it is of critical importance to examine the consequences of the co-occurance of stress and methamphetamine use. Activity of the glutamatergic N-methyl D-aspartate (NMDA) receptor system appears to be involved in the neurotoxic effects of both chronic stress and methamphetamine exposure. The current studies investigated the hypothesis that chronic pre-exposure to the stress hormone corticosterone (CORT) results in an increase of NMDA receptor activity and that this will potentiate the neurotoxic effects of methamphetamine (METH). Co-cultures of the …

Progress Towards Understanding Of Mechanisms Of Action Of Potent Multifunctional Disease Modifying Therapeutics For Parkinson's Disease & Investigating The Methamphetamine-Induced Striatal Microglia Activation., Mrudang M. Shah

Wayne State University Dissertations

PROGRESS TOWARDS UNDERSTANDING OF MECHANISMS OF ACTION OF POTENT MULTIFUNCTIONAL DISEASE MODIFYING

THERAPEUTICS FOR PARKINSON'S DISEASE.

by

MRUDANG MANOJKUMAR SHAH

December 2013

Advisor: Dr. Aloke Dutta

Major: Pharmaceutical Sciences

Degree: Doctor of Philosophy

Our long term goal is to design and develop potent multifunctional disease modifying therapeutics for Parkinson's disease. The objective of my dissertation was to understand the mechanisms of action of some potent small molecules (synthesized in our lab) as a disease modifying Parkinson's disease therapeutic. The objective was achieved by pursuing the following two specific aims:

1. Investigating anti-oxidant and neuroprotective effects of a lead molecule (D-512) …

Effects Of Methamphetamine On Sexual Behavior, Karla S. Frohmader

Electronic Thesis and Dissertation Repository

Methamphetamine (Meth) is a highly addictive psychostimulant associated with enhanced sexual desire, arousal, and sexual pleasure. Moreover, Meth abuse is frequently linked with the practice of sexual risk behavior and increased prevalence of Human Immunodeficiency Virus (HIV). Currently, the neurobiological basis for this drug-sex nexus is unknown. Moreover, there is a lack of studies investigating the effects of Meth on sexual behavior and more importantly, compulsive sex-seeking behavior, under controlled experimental settings in animal models. First, using immuhistochemistry for mating- and Meth-induced neural activation it was demonstrated that Meth administration in male rats activates neurons in brain regions of the …

Mitochondrial Fragmentation Is Involved In Methamphetamine-Induced Cell Death In Rat Hippocampal Neural Progenitor Cells., Changhai Tian, L. Charles Murrin, Jialin C. Zheng

Journal Articles: Pharmacology & Experimental Neuroscience

Methamphetamine (METH) induces neurodegeneration through damage and apoptosis of dopaminergic nerve terminals and striatal cells, presumably via cross-talk between the endoplasmic reticulum and mitochondria-dependent death cascades. However, the effects of METH on neural progenitor cells (NPC), an important reservoir for replacing neurons and glia during development and injury, remain elusive. Using a rat hippocampal NPC (rhNPC) culture, we characterized the METH-induced mitochondrial fragmentation, apoptosis, and its related signaling mechanism through immunocytochemistry, flow cytometry, and Western blotting. We observed that METH induced rhNPC mitochondrial fragmentation, apoptosis, and inhibited cell proliferation. The mitochondrial fission protein dynamin-related protein 1 (Drp1) and reactive oxygen …