Matching Items (39)
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Major Depressive Disorder (MDD) is a widespread mood disorder that affects more than 300 million people worldwide and yet, high relapse rates persist. This current study aimed to use an animal model for depression, unpredictable intermittent restraint (UIR), to investigate changes in a subset of neurons within the hippocampus, a

Major Depressive Disorder (MDD) is a widespread mood disorder that affects more than 300 million people worldwide and yet, high relapse rates persist. This current study aimed to use an animal model for depression, unpredictable intermittent restraint (UIR), to investigate changes in a subset of neurons within the hippocampus, a region of high susceptibility in MDD. Adult male and female Sprague-Dawley rats were randomly assigned to four treatment groups based on sex (n = 48, n = 12/group). Half of the rats underwent UIR that involved restraint with orbital shaking (30 min or 1 h) for 2-6 consecutive days, followed by one or two days of no stressors; the other half of the rats were undisturbed (CON). UIR rats were stressed for 28 days (21 days of actual stressors) before behavioral testing began with UIR continuing between testing days for nearly 70 days. Rats were then euthanized between 9 and 11 days after the last UIR session. Brains were processed for Golgi stain and long-shaft (LS) neurons within the hippocampal CA3a and CA3b regions were quantified for dendritic complexity using a Camera Lucida attachment. Our findings failed to support our hypothesis that UIR would produce apical dendritic retraction in CA3 hippocampal LS neurons in both males and females. Given that UIR failed to produce CA3 apical dendritic retraction in males, which is commonly observed in the literature, we discuss several reasons for these findings including, time from the end of UIR to when brains were sampled, and the effects of repeated cognitive testing. Given our published findings that UIR impaired spatial ability in males, but not females, we believe that UIR holds validity as a chronic stress paradigm, as UIR attenuated body weight gain in both males and females and produced reductions in thymus gland weight in UIR males. These findings corroborate UIR as an effective stressor in males and warrant further research into the timing of UIR-induced changes in hippocampal CA3 apical dendritic morphology.
ContributorsReynolds, Cindy Marie (Author) / Conrad, Cheryl D. (Thesis director) / Olive, M. Foster (Committee member) / School of Molecular Sciences (Contributor) / Department of English (Contributor) / Barrett, The Honors College (Contributor)
Created2020-12
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With opioid use disorder (OUD) being an epidemic, it is important to investigate the mechanisms as to why this is so. This study established a self-administration paradigm to model and investigate the mechanisms of polysubstance, sequential use in conjunction with the analysis of withdrawal symptomatology driven by opioid withdrawal. The

With opioid use disorder (OUD) being an epidemic, it is important to investigate the mechanisms as to why this is so. This study established a self-administration paradigm to model and investigate the mechanisms of polysubstance, sequential use in conjunction with the analysis of withdrawal symptomatology driven by opioid withdrawal. The independent variables were dichotomized into the control group (food/cocaine) and the experimental group (oxycodone/cocaine). We hypothesized that more cocaine would be self-administered on the first day of oxycodone withdrawal. In addition, we hypothesized that somatic signs of withdrawal would increase at 16 hours post-oxycodone self-administration. Finally, we hypothesized that cocaine intake during oxycodone withdrawal would potentiate subsequent oxycodone self-administration. Our findings revealed that animals readily discriminated between the active (food or oxycodone) and inactive levers - but will however require more animals to achieve the appropriate power. Further, the average cocaine infusions across phases exhibited significance between the oxycodone/cocaine and food/cocaine group, with the average cocaine infusions being lower in food than in oxycodone-experienced animals. This implies that the exacerbation of the sequential co-use pattern in this case yields an increase in cocaine infusions that may be driven by oxycodone withdrawal. Further, to characterize withdrawal from oxycodone self-administration, somatic signs were examined at either 0 or 16 hrs following completion of oxycodone self-administration. The oxycodone/cocaine group exhibited significantly lower body temperature at 16 hrs of oxycodone withdrawal compared to 0 hrs. No differences in somatic signs of withdrawal in the food/cocaine group was found between the two timepoints. Oxycodone withdrawal was not found to potentiate any subsequent self-administration of oxycodone. Future research is needed to uncover neurobiological underpinnings of motivated polysubstance use in order to discover novel pharmacotherapeutic treatments to decrease co-use of drugs of abuse. Overall, this study is of importance as it is the first to establish a working preclinical model of a clinically-relevant pattern of polysubstance use. By doing so, it enables an exceptional opportunity to examine co-use in a highly-controlled setting.
ContributorsUlangkaya, Hanaa Corsino (Author) / Gipson-Reichardt, Cassandra (Thesis director) / Olive, M. Foster (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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Alzheimer’s disease (AD) is a progressive cognitive and behavior disorder that is characterized by the deposition of extracellular Aβ plaques, intracellular neurofibrillary tangles, and neuroinflammation. Aβ is generated by cleavage of the amyloid precursor protein (APP) by β-secretase (BACE1) and, subsequently, y- secretase. In recent years, there has been an

Alzheimer’s disease (AD) is a progressive cognitive and behavior disorder that is characterized by the deposition of extracellular Aβ plaques, intracellular neurofibrillary tangles, and neuroinflammation. Aβ is generated by cleavage of the amyloid precursor protein (APP) by β-secretase (BACE1) and, subsequently, y- secretase. In recent years, there has been an increasing interest in studying and understanding inflammation as a therapeutic target for AD. Inflammation manifests in the brain in the form of activated microglia and astrocytes. These cells are able to release high levels of inflammatory cytokines such as Tumor Necrosis Factor-α (TNF-α). TNF-α is a major cytokine, which is involved in early inflammatory events and plays a role in the progression of AD pathology. There are currently no treatments that target chronic neuroinflammation. However, previous work in our laboratory with transgenic mice modeling AD suggested that the anti-cancer drug lenalidomide could lower neuroinflammation and slow AD progression, though the cellular and molecular mechanisms are yet to be elucidated. Here we hypothesized that lenalidomide can modulate TNF-α production in microglia and decrease amyloidogenesis. Using immortal cell lines mimicking several brain cell types, we discovered that lenalidomide is likely to decrease inflammation by modulating microglia cells rather than neurons or astrocytes. In addition, the drug may prevent the overexpression of BACE1 upon inflammation, thus blocking the overproduction of Aβ. If confirmed, these results could lead to a better understanding of how inflammation regulates Aβ synthesis and provide novel cellular and molecular therapeutic targets to control the progression AD.
ContributorsGujju, Manasa (Author) / DeCourt, Boris (Thesis director) / Olive, M. Foster (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Nicotine addiction remains a prevalent public health issue, and the FDA has released a statement outlining the systematic reduction of nicotine to non-zero levels in the coming years. Current research has not yet established the effects of abrupt nicotine dose reduction on vulnerability to relapse, nor has abrupt nicotine dose

Nicotine addiction remains a prevalent public health issue, and the FDA has released a statement outlining the systematic reduction of nicotine to non-zero levels in the coming years. Current research has not yet established the effects of abrupt nicotine dose reduction on vulnerability to relapse, nor has abrupt nicotine dose reduction been evaluated in terms of behavioral economic characteristics of demand and elasticity been evaluated for reduced doses of nicotine. Using a rat model, we first evaluated the comparability of between- and within-session protocols for establishing characteristics of demand and elasticity for nicotine to shorten experimental timelines for this study and future studies. We then tested environmental enrichment and sex as factors of elasticity of demand for nicotine. Using a rat model of relapse to cues, we also examined the effects of nicotine dose-reduction on vulnerability to relapse. We found differences in maximum consumption and demand between the between- and within-session protocols, as well as sex differences in elasticity of demand on the within-session protocol where male demand was more elastic than female demand. Additionally, we found that enrichment significantly increased elasticity of demand for nicotine for both males and females. Finally, preliminary analyses revealed that nicotine dose reduction yields more inelastic demand and higher maximum consumption, and these outcomes predict increased time to extinction of the association between nicotine and contingent cues, and increased rates of relapse. These studies highlight the usefulness and validity of within-session protocols, and also illustrate the necessity for rigorous testing of forced dose reduction on nicotine vulnerability.
ContributorsCabrera-Brown, Gabriella Paula (Author) / Gipson-Reichardt, Cassandra (Thesis director) / Olive, M. Foster (Committee member) / Davis, Mary (Committee member) / Sanford School of Social and Family Dynamics (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
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Cases of heroin use and overdose are on the rise in the United States which has created what some call a public health crisis. Previous studies have investigated the beneficial effect of social interaction recovering addicts, and in animal models of addiction, social interaction can prevent or reverse the conditioned

Cases of heroin use and overdose are on the rise in the United States which has created what some call a public health crisis. Previous studies have investigated the beneficial effect of social interaction recovering addicts, and in animal models of addiction, social interaction can prevent or reverse the conditioned rewarding effects of cocaine. This study sought to determine if social interaction would prevent or diminish a conditioned preference for a heroin-paired context. Following establishment of baseline place preference, adult male Sprague-Dawley rats underwent once daily conditioning with either saline, heroin (1 mg/kg), or the animal's cage-mate for a total of 8 conditioning sessions. Assessment of post-conditioning place preference revealed that both the heroin injections and the presence of the cage-mate produced a place preference . In contrast to the findings of previous studies using cocaine as the conditioning drug, it was determined that rats preferred the heroin-paired context over that paired with the cage-mate.. These findings suggest that the protective effects of social interaction found in prior studies using cocaine as the conditioning drug may not extend to opiates, perhaps a result of stronger contextual conditioning and/or rewarding effects of this class of abused drugs.
ContributorsMarble, Krista Lillian (Author) / Olive, M. Foster (Thesis director) / Tomek, Seven (Committee member) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
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The RAS/MAPK (RAS/Mitogen Activated Protein Kinase) pathway is a highly conserved, canonical signaling cascade that is highly involved in cellular growth and proliferation as well as cell migration. As such, it plays an important role in development, specifically in development of the nervous system. Activation of ERK is indispensable for

The RAS/MAPK (RAS/Mitogen Activated Protein Kinase) pathway is a highly conserved, canonical signaling cascade that is highly involved in cellular growth and proliferation as well as cell migration. As such, it plays an important role in development, specifically in development of the nervous system. Activation of ERK is indispensable for the differentiation of Embryonic Stem Cells (ESC) into neuronal precursors (Li z et al, 2006). ERK signaling has also shown to mediate Schwann cell myelination of the peripheral nervous system (PNS) as well as oligodendrocyte proliferation (Newbern et al, 2011). The class of developmental disorders that result in the dysregulation of RAS signaling are known as RASopathies. The molecular and cell-specific consequences of these various pathway mutations remain to be elucidated. While there is evidence for altered DNA transcription in RASopathies, there is little work examining the effects of the RASopathy-linked mutations on protein translation and post-translational modifications in vivo. RASopathies have phenotypic and molecular similarities to other disorders such as Fragile X Syndrome (FXS) and Tuberous Sclerosis (TSC) that show evidence of aberrant protein synthesis and affect related pathways. There are also well-defined downstream RAS pathway elements involved in translation. Additionally, aberrant corticospinal axon outgrowth has been observed in disease models of RASopathies (Xing et al, 2016). For these reasons, this present study examines a subset of proteins involved in translation and translational regulation in the context of RASopathy disease states. Results indicate that in both of the tested RASopathy model systems, there is altered mTOR expression. Additionally the loss of function model showed a decrease in rps6 activation. This data supports a role for the selective dysregulation of translational control elements in RASopathy models. This data also indicates that the primary candidate mechanism for control of altered translation in these modes is through the altered expression of mTOR.
ContributorsHilbert, Alexander Robert (Author) / Newbern, Jason (Thesis director) / Olive, M. Foster (Committee member) / Bjorklund, Reed (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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Evidence from the 20th century demonstrated that early life stress (ELS) produces long lasting neuroendocrine and behavioral effects related to an increased vulnerability towards psychiatric illnesses such as major depressive disorder, post-traumatic stress disorder, schizophrenia, and substance use disorder. Substance use disorders (SUDs) are complex neurological and behavioral psychiatric illnesses.

Evidence from the 20th century demonstrated that early life stress (ELS) produces long lasting neuroendocrine and behavioral effects related to an increased vulnerability towards psychiatric illnesses such as major depressive disorder, post-traumatic stress disorder, schizophrenia, and substance use disorder. Substance use disorders (SUDs) are complex neurological and behavioral psychiatric illnesses. The development, maintenance, and relapse of SUDs involve multiple brain systems and are affected by many variables, including socio-economic and genetic factors. Pre-clinical studies demonstrate that ELS affects many of the same systems, such as the reward circuitry and executive function involved with addiction-like behaviors. Previous research has focused on cocaine, ethanol, opiates, and amphetamine, while few studies have investigated ELS and methamphetamine (METH) vulnerability. METH is a highly addictive psychostimulant that when abused, has deleterious effects on the user and society. However, a critical unanswered question remains; how do early life experiences modulate both neural systems and behavior in adulthood? The emerging field of neuroepigenetics provides a potential answer to this question. Methyl CpG binding protein 2 (MeCP2), an epigenetic tag, has emerged as one possible mediator between initial drug use and the transition to addiction. Additionally, there are various neural systems that undergo long lasting epigenetics changes after ELS, such as the response of the hypothalamo-pituitary-adrenal (HPA) axis to stressors. Despite this, little attention has been given to the interactions between ELS, epigenetics, and addiction vulnerability. The studies described herein investigated the effects of ELS on METH self-administration (SA) in adult male rats. Next, we investigated the effects of ELS and METH SA on MeCP2 expression in the nucleus accumbens and dorsal striatum. Additionally, we investigated the effects of virally-mediated knockdown of MeCP2 expression in the nucleus accumbens core on METH SA, motivation to obtain METH under conditions of increasing behavioral demand, and reinstatement of METH-seeking in rats with and without a history of ELS. The results of these studies provide insights into potential epigenetic mechanisms by which ELS can produce an increased vulnerability to addiction in adulthood. Moreover, these studies shed light on possible novel molecular targets for treating addiction in individuals with a history of ELS.
ContributorsLewis, Candace (Author) / Olive, M. Foster (Thesis advisor) / Hammer, Ronald (Committee member) / Neisewander, Janet (Committee member) / Sanabria, Federico (Committee member) / Arizona State University (Publisher)
Created2015
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Description

Trees serve as a natural umbrella to mitigate insolation absorbed by features of the urban environment, especially building structures and pavements. For a desert community, trees are a particularly valuable asset because they contribute to energy conservation efforts, improve home values, allow for cost savings, and promote enhanced health and

Trees serve as a natural umbrella to mitigate insolation absorbed by features of the urban environment, especially building structures and pavements. For a desert community, trees are a particularly valuable asset because they contribute to energy conservation efforts, improve home values, allow for cost savings, and promote enhanced health and well-being. The main obstacle in creating a sustainable urban community in a desert city with trees is the scarceness and cost of irrigation water. Thus, strategically located and arranged desert trees with the fewest tree numbers possible potentially translate into significant energy, water and long-term cost savings as well as conservation, economic, and health benefits. The objective of this dissertation is to achieve this research goal with integrated methods from both theoretical and empirical perspectives.

This dissertation includes three main parts. The first part proposes a spatial optimization method to optimize the tree locations with the objective to maximize shade coverage on building facades and open structures and minimize shade coverage on building rooftops in a 3-dimensional environment. Second, an outdoor urban physical scale model with field measurement is presented to understand the cooling and locational benefits of tree shade. The third part implements a microclimate numerical simulation model to analyze how the specific tree locations and arrangements influence outdoor microclimates and improve human thermal comfort. These three parts of the dissertation attempt to fill the research gap of how to strategically locate trees at the building to neighborhood scale, and quantifying the impact of such arrangements.

Results highlight the significance of arranging residential shade trees across different geographical scales. In both the building and neighborhood scales, research results recommend that trees should be arranged in the central part of the building south front yard. More cooling benefits are provided to the building structures and outdoor microclimates with a cluster tree arrangement without canopy overlap; however, if residents are interested in creating a better outdoor thermal environment, open space between trees is needed to enhance the wind environment for better human thermal comfort. Considering the rapid urbanization process, limited water resources supply, and the severe heat stress in the urban areas, judicious design and planning of trees is of increasing importance for improving the life quality and sustaining the urban environment.

ContributorsZhao, Qunshan (Author) / Wentz, Elizabeth (Thesis advisor) / Sailor, David (Committee member) / Wang, Zhi-Hua (Committee member) / Arizona State University (Publisher)
Created2017
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Use of psychostimulants, such as cocaine, is associated with an increased risk of human immunodeficiency virus (HIV) infection. Dopaminergic signaling within the nucleus accumbens (NAc) is critically implicated in both disease states, mediating the addictive and reinforcing effects of cocaine and perpetuating HIV replication throughout the central nervous system (CNS).

Use of psychostimulants, such as cocaine, is associated with an increased risk of human immunodeficiency virus (HIV) infection. Dopaminergic signaling within the nucleus accumbens (NAc) is critically implicated in both disease states, mediating the addictive and reinforcing effects of cocaine and perpetuating HIV replication throughout the central nervous system (CNS). Cocaine and HIV induce neurobehavioral deficits separately; however, little is known regarding how they interact to dysregulate neuroimmune function or how this impacts relapse vulnerability. We have previously shown that inhibition of dopamine D3 receptor (D3R) signaling using MC-25-41, a novel and highly selective D3R partial agonist, attenuates cocaine-seeking behavior. Here, we sought to characterize changes in neuroimmune function in a rat model of combined HIV and cocaine use disorders across abstinence and examined the therapeutic efficacy of MC-25-41 in the presence of this comorbidity. Male rats were systemically treated with the HIV protein gp120 after establishing a history of cocaine self-administration and then, following 21 days of abstinence, were administered a systemic injection of MC-25-41 (10 mg/kg) prior to cue reactivity testing. Glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (Iba1) immunoreactivity were analyzed after 5 or 21 days of cocaine abstinence as an index of glial cell levels. We demonstrate that inhibition of D3R signaling significantly attenuates cue-induced cocaine seeking among control rats but not gp120-exposed rats. Moreover, we show that NAc core GFAP and Iba1 expression is impaired by 5 days of abstinence, which persists into protracted abstinence and cue reactivity testing. However, we also demonstrate that neither gp120 nor D3R inhibition significantly altered NAc core GFAP or Iba1 expression. Altogether, these results reveal significant changes in glial cell function across cocaine abstinence and unique behavioral interactions with gp120 may inhibit the effectiveness of medication regimens, which highlights the need to consider these comorbidities when treating HIV infection.

ContributorsPhillips, Megan (Author) / Neisewander, Janet (Thesis director) / Olive, M. Foster (Committee member) / Namba, Mark (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2021-12
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Studies on urban heat island (UHI) have been more than a century after the phenomenon was first discovered in the early 1800s. UHI emerges as the source of many urban environmental problems and exacerbates the living environment in cities. Under the challenges of increasing urbanization and future climate changes, there

Studies on urban heat island (UHI) have been more than a century after the phenomenon was first discovered in the early 1800s. UHI emerges as the source of many urban environmental problems and exacerbates the living environment in cities. Under the challenges of increasing urbanization and future climate changes, there is a pressing need for sustainable adaptation/mitigation strategies for UHI effects, one popular option being the use of reflective materials. While it is introduced as an effective method to reduce temperature and energy consumption in cities, its impacts on environmental sustainability and large-scale non-local effect are inadequately explored. This paper provides a synthetic overview of potential environmental impacts of reflective materials at a variety of scales, ranging from energy load on a single building to regional hydroclimate. The review shows that mitigation potential of reflective materials depends on a set of factors, including building characteristics, urban environment, meteorological and geographical conditions, to name a few. Precaution needs to be exercised by city planners and policy makers for large-scale deployment of reflective materials before their environmental impacts, especially on regional hydroclimates, are better understood. In general, it is recommended that optimal strategy for UHI needs to be determined on a city-by-city basis, rather than adopting a “one-solution-fits-all” strategy.

ContributorsYang, Jiachuan (Author) / Wang, Zhi-Hua (Author) / Kaloush, Kamil (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2015-07-01