Neuroscience and Neurobiology Commons^™

Estrogen Replacement Therapy To Reduce Neurodegeneration And Socio-Cognitive Deficits In A Female Sprague Dawley Rat Model Of Early-Onset Alzheimer’S Disease, Miriam Kirylo

Senior Theses and Projects

No abstract provided.

Pipecolic Acid And Novel Insights Into Cerebral Malaria, Akua E. Mensah

Theses

Cerebral malaria (CM), a severe manifestation of Plasmodium infection, prompts our investigation into the nuanced role of pipecolic acid in its pathophysiology. To unravel the molecular intricacies, we conducted in vitro lysine labeling techniques of mice infected with P. berghei ANKA parasites, and human P. falciparum grown in vitro, aiming to discern the impact of Plasmodium on pipecolic acid production. Previous observations indicated an elevation in pipecolic acid levels correlating with neurological decline in children with CM. In our study, confirming elevated pipecolic acid presence in the plasma and brain tissues of CM patients and the animal model of CM, …

Vapourized Cannabis Extract Administration Impairs Memory And Alters Neural Activity In Laboratory Rats, Megan Chladny

Theses and Dissertations (Comprehensive)

Although people have smoked cannabis for millennia, administration of cannabis by heating the dried plant material or distilled extracts to a temperature just below the combustion point (i.e., vapourization or "vaping") has rapidly increased over the past few years (Javadi-Payder, Cole, and Taffe, 2018; Manwell, Charchoglyan, Brewer, Matthews, Heipel, and Mallet, 2014). Conversely, most of the cannabinoid research using rodent models has used parenteral routes of administration to examine the effects of purified cannabis extracts such as ∆⁹-tetrahydrocannabinol (THC), making it difficult to directly compare laboratory research to human drug use. Building on previous studies showing that THC …

Morphine-Induced Tolerance Is Reduced By The Consumption Of A Ketogenic Diet, But Not A High Fat/High Carbohydrate Diet, Nina Beltran

Open Access Theses & Dissertations

Opioid drugs like morphine are used medicinally for pain relief, but also have abuse liability that can lead to opioid use disorder (OUD), which contributes to nearly 70% of drug overdose deaths in the United States. Another rising health concern is the global obesity epidemic, and new evidence suggests that obesity and OUD might converge to impact individuals. For example, high body mass index (BMI) is associated with greater reports of pain among women. Further, opioid overdose risk is increased among individuals diagnosed with obesity, suggesting a potential relationship that might convey enhanced vulnerability among some populations. Given the high …

Novel Therapeutic Strategies For Alzheimer’S Disease: Prostaglandin D2 Signaling And Its Human Polymorphisms As Well As A Polypharmacological Approach, Charles H. Wallace

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is an age related neurodegenerative disease with pathology that includes amyloid plaques, neurofibrillary tangles and non-resolving neuroinflammation. Non-resolving neuroinflammation lasts the entire course of the disease and has deleterious effects and is often thought to accelerate AD pathology. Non-Steroidal Anti-inflammatory Drugs (NSAIDs) have commonly been used as therapeutics to treat pain, inflammation and vascular. NSAIDs work by altering the cyclooxygenase (COX) mediated biosynthesis of prostaglandins which are lipid mediators that have many physiological functions, for example nociception, inflammation and vasodilation. Epidemiological studies support the notion that NSAIDs could be used to treat AD. Yet, clinical trials using …

A Polypharmacological Approach To Relapse Prevention In An Animal Model Of Heroin Addiction, Scott T. Ewing

Dissertations, Theses, and Capstone Projects

Chemical compounds that target dopamine (DA) D1 or D3 receptors have shown promise as potential interventions in animal models of cue-induced relapse. However, undesirable side effects or pharmacodynamic profiles have limited the advancement of new compounds in preclinical studies when administered as independent treatments. In this series of experiments, we explored the effects of co-administration of a D1-recepter partial agonist (SKF 77434) and a D3-receptor antagonist (NGB 2904) in heroin-seeking rats within a ‘conflict’ model of abstinence and cue-induced relapse. Rats were first trained to press a lever to self-administer heroin and drug delivery was paired contingently with cues (e.g., …

Prefrontal Coding Of Naturalistic Working Memory: Mechanisms During Normal Maintenance And Modelled Disease, Megan P. Roussy

Electronic Thesis and Dissertation Repository

Neural activity in the primate lateral prefrontal cortex (LPFC) has been causally linked to working memory (WM) ⁠— the brief maintenance and mental manipulation of information. Primates use WM to perform tasks in complex contexts; however, neural mechanisms of WM and the pathophysiology related to WM deficits have traditionally been studied using simple tasks that deviate from naturalistic conditions. This raises the question, how is WM processed in naturalistic conditions? To explore this, I trained two macaque monkeys on a spatial WM task set in a naturalistic virtual environment. During the task, a target was presented in 1 of 9 …

Validation Of The 40 Hz Auditory Steady State Response As A Pharmacodynamic Biomarker Of Evoked Neural Synchrony, Muhammad Ummear Raza

Electronic Theses and Dissertations

Schizophrenia is a troubling and severe mental illness that is only incompletely treated by currently available drugs. New drug development is hindered by a scarcity of functionally relevant pharmacodynamic biomarkers that are translatable across preclinical and human subjects. Although psychosis is a major feature of schizophrenia, cognitive and negative symptoms determine the long-term functional outcomes for patients. Stimulus-evoked neural synchrony at gamma (~ 40 Hz) frequency plays an important role in the processing and integration of sensory information. Not surprisingly, schizophrenia patients show deficits in gamma oscillations. NMDA receptor (NMDAR) activation on fast-spiking parvalbumin-positive interneurons is deemed important for the …

Cortisol Receptor Sensitivity As A Risk Factor For Depression, Michela Michielli

Honors Theses

In 2020, the World Health Organization reported over 264 million people across the world were suffering from depression. Studies have demonstrated that one source of depression is a hormonal imbalance involved in the stress response. Cortisol is a stress hormone regulated by the Hypothalamic-Anterior-Pituitary (HPA) Axis. Its effects on the stress response and other metabolic activities in the body are exerted through the glucocorticoid and mineralocorticoid receptors (GR and MR respectively).

Our research has examined mutations known as single-nucleotide-polymorphisms (SNPs) relating to cortisol-receptor sensitivity and the behavior of cortisol in the body to investigate the link between cortisol activity and …

Sex-Specific Effects Of Chaperone And Glial Defenses On Experimental Lewy Body Disease, Tarun Bhatia

Electronic Theses and Dissertations

Lewy body disorders are a group of neurodegenerative conditions characterized by the pathological misfolding and aggregation of the abundant protein, α-synuclein. The most common Lewy body disorders are Parkinson’s disease and dementia with Lewy bodies. Apart from ageing, male sex is a major risk factor for Lewy body disorders, as men are at ~1.5-fold higher risk for these diseases than women. Yet, preclinical studies on Lewy body disorders rarely examine sex as a biological variable, and the mechanisms underlying sex-skewedness in disease risk remain undetermined.

Here, we developed a sex-stratified model of Lewy body disorders by exposing primary neurons harvested …

Behavioral Effects And Neurobiological Mechanisms Of 3-Aminobenzimide In A Rodent Model Of Chronic Psychological Stress, Liza Wills

Electronic Theses and Dissertations

Major depressive disorder (MDD) is a leading cause of disability worldwide, with a lifetime prevalence rate of approximately 20%. Inadequate pharmacological treatment methods for MDD are a significant debilitating factor. Patient estimates suggest that the treatment resistance rate for pharmacological interventions is over 30%. Postmortem analyses of human tissue of individuals diagnosed with MDD have shown an increase in Poly (ADP-ribose) polymerase 1 (PARP-1) mRNA gene expression in prefrontal cortical white matter when compared to psychiatrically normal brain tissue. In order to further investigate this issue, the present study used the social defeat stress/chronic unpredictable stress (SDS + CUS) rodent …

Exploiting Modulation Of The Blood-Brain And Blood-Tumor Barrier Permeability By Translational Focused Ultrasound For Therapeutic Delivery To Cns Metastases, Tasneem A. Arsiwala

Graduate Theses, Dissertations, and Problem Reports

Transcranial low-intensity focused ultrasound is a unique technology to modulate the integrity of tight endothelial junctions and transiently increase BBB/BTB permeability to enhance therapeutic delivery. Despite promising early studies, present literature lacks agreement on key experimental conditions, which restricts our knowledge and the technique's widespread translation. This dissertation first provides a critical review of the current gaps in knowledge regarding the universal use of LiFUS in preclinical and clinical use. We then identify key parameters for translational and predictable opening of the BBB using a 3T MRI coupled with a clinical device. Our investigation highlights that passive permeability of the …

Psychedelics Can Save: The Scientific And Social Case For Rescheduling Psychedelic Compounds, Galen M. Fader

Chancellor’s Honors Program Projects

No abstract provided.

Use Of A Zebrafish Model To Identify Anticonvulsant Properties Of Cannabinoid And Terpenoid Extracts And Mixtures, Courtney Murr

LSU Master's Theses

Epilepsy is a complex group of neurological disorders affecting approximately 65 million people worldwide. Animal models reveal the activation of cannabinoid receptor 1 and cannabinoid receptor 2 reduces the severity of seizures associated with epilepsy. Trials of phytocannabinoids in mammals demonstrate their efficacy of reducing the severity of epileptic seizures. Numerous terpenoid compounds are present in Cannabis plants but most have yet to be clinically investigated. The goal of this research was to use zebrafish (Danio rerio) to identify the potential anticonvulsive properties of phytocannabinoid and terpenoid compounds. During acute cannabinoid exposures, 7-days-post-fertilization (7 dpf) zebrafish larvae were …

Network And Cellular Effects Of The Mu Opioid Receptor In Cortical Interneurons, Adrian Dutkiewicz

Graduate College Dissertations and Theses

The µ opioid receptor (µOR) exerts a powerful excitatory effect in cortical circuits and cultured neurons by promoting glutamatergic activity after binding endogenous or exogenous opioids. While most research indicates that the receptor does this by decreasing activity or output of GABAergic interneurons that inhibit glutamate-releasing Pyramidal Neurons, other experiments suggest that the µOR directly upregulates excitatory Pyramidal Neurons instead. Thus, the cellular target of cortical opioid agonists remains unclear, and the µOR’s net excitatory mechanisms are not fully understood. Consequently, utilizing electrophysiology to detect µOR responses to the specific agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin (DAMGO) has yielded incomplete information on …

Investigating Cannabinoid Type-1 Receptor (Cb1r) Positive Allosteric Modulators (Pams) In Mouse Models Of Overt Cannabimimetic Activity, Subjective Drug Effects, And Neuropathic Pain, Jayden Elmer

Theses and Dissertations

Chronic pain affects between 20 and 30 percent of the adult population in western countries and represents a wide array of specific etiologies (Berge, 2011). Neuropathic pain secondary to traumatic nerve injury, chemotherapeutic toxicity, or diseases (e.g., diabetes mellitus) is often refractory to conventional analgesics, with patients receiving less than 50% pain relief compared to placebo (Finnerup et al. 2010). The endocannabinoid system has shown potential as a therapeutic target for neuropathic pain wherein CB1 agonism via administration of exogenous agonists or pharmacological blockade of endocannabinoid catabolic enzymes exhibits efficacy in reversing allodynia in the chronic constriction injury (CCI) model …

Interclass Gpcr Heteromerization Affects Localization And Trafficking, Rudy Toneatti

Theses and Dissertations

Class A serotonin (5-hydroxytryptamine) 2A (5-HT_2AR) and class C metabotropic glutamate 2 receptors (mGluR2) are seven transmembrane receptors (7TMRs or G protein-coupled receptors – GPCRs) involved in multiple neuropsychiatric disorders including schizophrenia. Previous findings from our laboratory reported that 5-HT_2AR and mGluR2 are dysregulated in the prefrontal cortex of patients suffering from this psychiatric condition, although 5-HT_2AR’s expression was recovered in antipsychotic-medicated patients. Genome-wide association studies on schizophrenia reported that endosomal trafficking that regulates cell surface abundance of another 7TMR implicated in this disease (dopamine D2 receptor) can be altered. Ligand-activated receptors, including the …

Morphological Changes In Dorsal Root Ganglia Macrophages Associated With Neuropathic Pain Mechanisms Suggest A Novel Target For Chronic Pain Therapy, Emily Kussick

CMC Senior Theses

The present study examined morphological changes in the dorsal root ganglia (DRG) following an innate immune stimulus. The importance of the DRG has increasingly become recognized in pain processing as more than just the home of primary afferent cell bodies. All sensory information passes through the DRG via the primary afferents, and on to the spinal cord. The primary afferents synapse with second-order neurons in the spinal cord that ascend towards the brain, where they transmit the pain signal to the limbic forebrain and/or the somatosensory cortex for processing. The DRG is an interesting niche to study at as it …

Opioids Disrupt Sleep And Wakefulness In C57bl/6j Mice, Clarence E. Locklear

Masters Theses

Opioid use disorder (OUD) is a major public health burden. According to the National Institutes of Health (NIH), studies helping to understand the mechanisms of OUD will help improve prevention and treatment. Opioids long have been shown to disrupt sleep and sleep disruption enhances the likelihood of addiction relapse in humans. The NIH refers to the mouse as one of the most powerful animal systems to study because of the genetic homologies between human and mouse. Prior to the present research, no studies have quantified the effect of opioids on states of sleep and wakefulness in mice. The current study …

Hiv-1 Tat Interactions With Opioids Are Modulated By Progesterone And Estradiol, Dejun Jackson

Honors Theses

HIV infection and combined substance abuse are comorbid epidemics. Previous studies show that concurrent opioid drug use may potentiate HIV-1-mediated neurotoxicity partly via interactions with opioids. Preclinical studies suggest that the HIV-1 trans-activator of transcription (Tat), an HIV regulatory protein, can synergize with opioids to exacerbate its already neurotoxic effects. However, its interactions with clinical opioids, such as oxycodone, have yet to be elucidated. Additionally, Tat disrupts a number of systems including the dopaminergic system, which contribute to its capacity to potentiate the rewarding effects of abused drugs. Although the neurotoxic effects of Tat may be inhibited by gonadal steroids …

Levels Of Parp1-Immunoreactivity In The Human Brain In Major Depressive Disorder, Aamir Shaikh

Undergraduate Honors Theses

MDD is a severe and debilitating disorder that is associated with a growing global economic burden due to reduced workplace productivity along with increased healthcare resource utilization. Furthermore, depression markedly enhances the risk for suicide, mortality that is especially worrisome given that 30% of depressed individuals have an inadequate response to current antidepressants. This inadequacy of antidepressants necessitates the discovery of a better understanding of the pathobiology of MDD. Most current antidepressants work through monoamine neurotransmitters, and their relative efficacy in depression led to the now dated monoamine-deficiency hypothesis. The limited usefulness of antidepressants has led to a reinvigorated search …

Activation Of The Sonic Hedgehog Effector Smoothened Counteracts L-Dopa Induced Dyskinesia By Restoring Cholinergic Interneuron Function, Lauren Malave

Dissertations, Theses, and Capstone Projects

Many types of neurons act as multimodal signaling centers. Yet, we have only limited insight into the regulation and functional consequences of neuronal co-transmission. For example, dopamine (DA) neurons, whose degeneration causes motor deficits characteristic of Parkinson’s Diseases (PD), communicate with all their targets by DA but only a selective subset of their targets using GABA, Glutamate, and the secreted cell signaling protein Sonic Hedgehog (Shh). It is unknown whether Levo-dopamine (L-Dopa) induced dyskinesia (LIDs), a severely debilitating side effect of DA supplementation in PD, might appear because DA neuron targets are exposed to high DA- but low Shh- signaling …

Sex Differences In The Mechanisms That Modulate The Neurochemical Effects Of Nicotine, Kevin Uribe

Open Access Theses & Dissertations

Prior behavioral studies in our laboratory revealed that overexpression of the stress peptide, corticotrophin-releasing factor (CRF), in the mesocorticolimbic reward pathway enhanced the reinforcing effects of nicotine. The latter effect was greater in female versus male rats, suggesting that females are uniquely susceptible to the effects of stress on nicotine reinforcement. The goal of this dissertation was to examine the neurochemical mechanisms by which overexpression of CRF in the nucleus accumbens (NAc), a terminal region of the mesocorticolimbic pathway, modulates the behavioral effects of nicotine. Specifically, we examined whether nicotine-induced dopamine levels are altered by CRF overexpression via excitatory (glutamate) …

Combination Of Investigational Cell-Based Therapy And Deep Brain Stimulation To Alter The Progression Of Parkinson’S Disease, Nader El Seblani

Theses and Dissertations--Pharmacy

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the motor symptoms are caused by progressive loss of midbrain dopamine neurons. There is no current treatment that can slow or reverse PD. Our current “DBS-Plus” clinical trial (NCT02369003) features the implantation in vivo of autologous Schwann cells (SCs) derived from a patient’s sural nerve into the substantia nigra pars compacta (SNpc) in combination with Deep Brain Stimulation (DBS) therapy for treating patients with advanced PD.

The central hypothesis of our research is that transdifferentiated SCs within conditioned nerve tissue will deliver pro-regenerative factors to enhance the survival of …

Finding Brain Predictors Of Psychostimulant Medication Use In Adhd Using Machine Learning, Zoe Irene Hulce

Graduate College Dissertations and Theses

Psychostimulant medication is the first line of treatment for Attention deficit/hyperactivity disorder (ADHD). Despite the prevalence of ADHD, there is a lack of understanding of the underlying neurophysiological mechanisms of the disorder and its pharmacological treatments. Existing neuroimaging research shows some consistent structural differences in ADHD, but it can be difficult to discern what is relevant. Machine learning algorithms present a novel way of analyzing a large amount of data by making predictions based on pattern detection.

The present study applied an elastic-net logistic machine learning model to structural magnetic resonance imaging (sMRI) data from the Adolescent Brain Cognitive Development …

Role Of Astrocyte-Derived Extracellular Vesicles In Neuroinflammation Mediated By Drug Abuse, Ke Liao

Theses & Dissertations

Neuronal damage and neuroinflammation is a hallmark feature of HIV-associated neurological disorders (HANDs). Opioids abuse accelerates the incidence and progression of HAND; however, the mechanisms underlying the potentiation of neuropathogenesis by these drugs remain elusive. Extracellular vesicles (EVs) are essential conduits in HIV and drug abuse-mediated synaptodendritic injury and neuroinflammation. Findings from our group have demonstrated that astrocyte-derived EV (ADEV)-miRNA-29b mediates HIV Tat and morphine-induced neuronal injury, thus underscoring the importance of such interactions in NeuroHIV.

Besides, HIV Tat and morphine-mediated synaptodendritic injury via ADEVs, we are also interested in whether ADEVs contributes to neuroinflammation. Microglia are critical players in …

Novel Antiviral Effect Of A Small Molecule Onc201 And Its Potential Application In Hiv-1 Eradication, Runze Zhao

Theses & Dissertations

Despite the success of antiretroviral therapy (ART), eradication of HIV-1 from brain reservoirs remains elusive. HIV-1 brain reservoirs include perivascular macrophages that are behind the blood-brain barrier and difficult to access by ART. Macrophages express transcription factor FOXO3a and the TNF superfamily cytokine TRAIL, which are known to target HIV-1-infected macrophages for viral suppression. ONC201 is a novel and potent FOXO3a activator capable of inducing TRAIL. It can cross the blood-brain barrier, and has shown an antitumor effect in clinical trials. We hypothesized that activation of FOXO3a/TRAIL by ONC201 will reduce the size of HIV-1 brain reservoirs. Using primary human …

Structure-Activity Relationship Studies Of Synthetic Cathinones And Related Agents, Rachel A. Davies

Theses and Dissertations

Synthetic cathinones and related agents represent an international drug abuse problem, and at the same time an important class of clinically useful compounds. Structure-activity relationship studies are needed to elucidate molecular features underlying the pharmacology of these agents. Illicit methcathinone (i.e., MCAT), the prototype of the synthetic cathinone class, exists as a racemic mixture. Though the differences in potency and target selectivity between the positional and optical isomers of synthetic cathinones and related agents have been demonstrated to have important implications for abuse and therapeutic potential, the two MCAT isomers have never been directly compared at their molecular targets: the …

Molecular Targets Of Psychedelics And Their Role In Behavioral Models Of Hallucinogenic Action, Hiba Z. Vohra

Theses and Dissertations

Psychedelics are a subset of hallucinogenic drugs that exert their characteristic effects through agonist activity at the serotonin receptor 2A (5-HT_2A). In this study, I aimed to characterize the modulatory role of the metabotropic glutamate subtype 2 receptor (mGluR2) in the 5-HT_2A-specific rodent model of hallucinogenic action, head-twitch response (HTR). Secondly, I aimed to explore if 5-HT_2A agonist-induced deficits in prepulse inhibition (PPI) of the startle response, an additional model of hallucinogenic action, could be produced in mice. Though 5-HT_2A agonist-induced PPI deficits, which represent interruptions in normal sensorimotor gating, have been described in …

The Metabotropic Glutamate Receptor Mglur1 Regulates The Voltage-Gated Potassium Channel Kv1.2 Through Agonist-Dependent And Agonist-Independent Mechanisms, Sharath Chandra Madasu

Graduate College Dissertations and Theses

The voltage gated potassium channel Kv1.2 plays a key role in the central nervous system and mutations in Kv1.2 cause neurological disorders such as epilepsies and ataxias. In the cerebellum, regulation of Kv1.2 is coupled to learning and memory. We have previously shown that blocking Kv1.2 by infusing its specific inhibitor tityustoxin-kα (TsTX) into the lobulus simplex of the cerebellum facilitates eyeblink conditioning (EBC) and that EBC itself modulates Kv1.2 surface expression in cerebellar interneurons. The metabotropic glutamate receptor mGluR1 is required for EBC although the molecular mechanisms are not fully understood. Here we show that infusion of the mGluR1 …