Molecular and Cellular Neuroscience Commons^™

Investigating The Neuroprotective Effects Of Cannabinoids And Insulin-Like Growth Factors On Glia With Induced Inflammation, Caleb Bloodworth

Honors Theses

Chronic inflammation is a driver of numerous neurodegenerative diseases that reduce quality of life for affected individuals. Non-psychoactive cannabinoids have begun to gain more interest in the world of anti-inflammatory medicine for chronically ill patients. Along with these cannabinoids, insulin-like growth factor-1 has been examined for its association with downregulation of inflammation. Our research aimed to investigate how neuroglia are affected by treatment with cannabinoids or IGF-1 in the face of inflammation from HIV-1 protein, Tat, or lipopolysaccharide (LPS). Preliminary studies in our laboratory showed that neither cannabinoids or IGF-1 treatment altered astrocyte morphology or overall astrocyte viability under baseline …

Innate Immunity In The Pathobiology And Treatment Of Infectious And Neurodegenerative Diseases, Mai Mostafa

Theses & Dissertations

Mononuclear phagocytes (MPs; monocytes, macrophages, and dendritic cells) are the governors of innate immunity which is the body’s first line of defense against microbial pathogens. They act beneficial or detrimental. They are crucial for an effective non-specific immune response to invading pathogens by engulfing, destroying, then eliciting an adaptive specific immune response. Given their pivotal functions in the host immune defense, studying MP immune responses in disease is paramount important for understanding disease pathobiology and uncovering therapeutic strategies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the driver of acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19) amongst …

Morphine-Induced Hyperactivity Is Attenuated By Intra-Accumbens Administration Of The Highly-Selective Dopamine D3 Receptor Antagonist Vk4-40, Mansi Patel, Desta M. Pulley, Daniel Manvich

Rowan-Virtua Research Day

Opioids exert their abuse-related effects by enhancing dopamine (DA) neurotransmission within the brain’s mesolimbic reward system, a neural projection involving DA neurons in the ventral tegmental area (VTA) that project to medium spiny neurons within the nucleus accumbens (NAc). Mu (MOR) are expressed by several populations of GABAergic neurons that tonically inhibit VTA DA neurons. By inhibiting these GABAergic neurons in a MOR-dependent manner, opioids indirectly enhance DA neurotransmission via disinhibition of DAergic neurons. Accumulating evidence indicates that selective pharmacological antagonism of the dopamine D3 receptor (D3R) attenuates the abuse-related effects of several opioids, but the neurobiological mechanisms mediating this …

Efficacy Of Δ-9-Tetrahydrocannabinol For Hiv-Related Neuropathic Pain, Kaia Horne

Honors Theses

Despite the availability and success of antiretroviral therapeutics, ~30% of patients living with HIV experience neuropathic pain that is often intractable. The mechanisms are not known, but there is evidence to support a role for the HIV virotoxins, Tat and/or gp120, which can damage or degenerate neurons and peripheral nerves. One mechanism by which Tat and gp120 promote nerve damage involves the stimulation of proinflammatory cytokine production from immune cells which can damage or kill bystander cells. Notably, compounds found in Cannabis exert anti-inflammatory effects and many studies report HIV patients to consume more marijuana than seronegative individuals. When people …

The Effects Of Deletion Of The Cytoplasmic Domain Of Robo3 On Drosophila, Jessie Agcaoili

Biological Sciences Undergraduate Honors Theses

My research project examines how the deletion of the cytoplasmic domain affects the function of Robo3. If Robo3 is signaling repulsion in response to SLIT this activity should require the cytoplasmic domain. I investigated the functional importance of Robo3 by deleting the cytoplasmic domain of Robo3 using a CRISPR-based technique. This modified gene was then injected into Drosophila embryos where it replaced the normal copy of the gene. Embryos expressing the modified version of robo3 in place of normal robo3 were dissected and examined.

Characterizing Rat Lateral Amygdala Interneurons By Colocalization Of Calcium-Binding Proteins Via Serial Multiplex Immunohistochemistry, Ethan Gasteyer

Honors Scholar Theses

The lateral amygdala is a brain structure that plays an important role in regulating fear and anxiety. Some anxiety disorders are hypothesized to develop from failures in this local inhibitory circuit. Distinct populations of these inhibitory neurons express patterns of calcium- binding proteins and neuropeptides that suggest differences in functionality within the lateral amygdala. Furthermore, these patterns of expression are compared between male and female rats to identify sex differences in the lateral amygdala. Previous studies have reported sex differences in amygdala activation and connectivity, but very little is known about the sexual dimorphism of calcium-binding protein and neuropeptide expression. …

Hypocretin-Receptor Mrna Expression In The Central Amygdala Of Alcohol-Dependent And Non-Dependent Rats, Gabriel Aldridge

Electronic Theses and Dissertations

Hypocretin/Orexin (HCRT) neurotransmission facilitates drug-seeking behavior. HCRT neurotransmission at HCRT-receptors 1 and 2 (HCRT-R1 and -R2, respectively) is implicated in addiction. During the shift to alcohol-dependency, adaptations in neurotransmitter systems occur in reward- and stress-related brain regions. Specifically, neurotransmission systems in the central amygdala (CeA) are modulated by alcohol drinking/exposure. Therefore, this study investigated Hcrtr1 and Hcrtr2 mRNA expression in the CeA of alcohol-dependent rats and in non-dependent controls during acute alcohol withdrawal. Fos mRNA expression in the CeA of alcohol-dependent and non-dependent rats was also determined to assess adaptations in neuronal activation. To our knowledge, this is the first …

Innate Lymphoid Cell Characterization And Ilc2s In Neuroinflammation In Aging And Sex Differences, Alexis Mobley, Alexis S. Mobley

Dissertations and Theses (Open Access)

Aging affects immunologic responses by a global immune system suppression, including dysregulation of cytokine mediators, leading to increased inflammation throughout all systems, termed inflammaging. However, understanding healthy aging mechanisms can bypass this effect. Inflammaging also leads to poor outcomes during brain injury, making immune-targeting therapeutics tantamount to overall brain health and longevity. Moreover, sex affects disease etiology and severity through hormonal and chromosomal sex, as the X chromosome contains most immunology-based genes. Androgens have a generally suppressive effect on the immune system. Additionally, when immune responses are mounted, males are better at CD4+ T cell type (Th1) responses, while females …

Vitamin D And Its In Vitro Therapeutic Action Mediated Through Vdr Rather Than Pdia3, Jaeden Pyburn

Undergraduate Honors Theses

Brain calcification is a common occurrence in the aging process, with >20% of individuals over the age of 65 showing hardened plaques in the basal ganglia. Loss of the vitamin D receptor (VDR) in transgenic mice leads to formation of calcified plaques in the basal ganglia and thalamus within the mice. Vitamin D signals through two known vitamin D responsive proteins, protein disulfide isomerase A3 (PDIA3) and VDR. In vitro, vitamin D has been demonstrated to suppress calcification in osteoblast-like cells. Here, we aim to elucidate which of either PDIA3 or VDR transduce vitamin D mediated suppression of calcification in …

The Relationship Between Circadian Rhythms And Neurodegenerative Disease, Christopher Simpson

Honors Projects

Neurodegenerative disease is a pervasive and insidious disease affecting a large proportion of the elderly population. Leading to the degeneration of neural tissue throughout the nervous system, it is a slow and progressive disorder. Because of its nature, it is possible that it has a connection to circadian rhythms. Circadian rhythms are the endogenous approximately 24-hour rhythms of the body commonly associated with the sleep-wake cycle, but they account for much more. This review aims to ascertain the relationship between the two by covering several facets of research pursued in the past five years. Beginning with establishing a basic understanding …

Alzheimer's Disease: A Comprehensive Review Including Personal Experience From Retirement Home Patients, Sydney Fox

Honors Theses

Alzheimer’s Disease is a neurodegenerative illness and disease, the most common type of dementia, and the sixth leading cause of death (Sá et al., 2012). The disease was discovered in 1906 and named after Dr. Alois Alzheimer, a psychiatrist and neuropathologist. Over time, a variety of hypotheses have developed regarding the cause behind this multifactorial disease, and these will be disclosed in a later section. Nonetheless, the disease was first observed in changes of the brain tissue of a woman who was said to have die from an unusual mental illness with many abnormal bumps. These bumps are now recognized …

Investigating The Role Of The Basolateral Amygdala Plays In The Incubation Of Cue-Induced Cocaine Seeking Behavior, Claire Marie Corbett

Graduate School of Biomedical Sciences Theses and Dissertations

Cocaine use disorder is a chronic, relapsing brain disease. Sex and ovarian hormones are known to influence cocaine addiction liability and relapse vulnerability. However, little is known regarding the cellular and synaptic mechanisms contributing to sex differences in relapse vulnerability, including how these measures are influenced by hormonal fluctuations. To investigate sex differences in relapse vulnerability we use a rodent model of cocaine craving and relapse called the incubation model in which cue-induced seeking progressively increases or “incubates” during the first month of withdrawal from extended-access cocaine self-administration. Using this model, we have recently shown that females in the estrus …

Trkb Activity Alters Voluntary Alcohol Consumption In Nondependent Mice, Alfred Amendolara

Annual Research Symposium

No abstract provided.

Novel Methodology For The Investigation Of Dmrt3a Interneurons In Larval Zebrafish, Alfred Amendolara

Annual Research Symposium

No abstract provided.

Prmt5 Interacting Partners And Substrates In Oligodendrocyte Lineage Cells, David K. Dansu, Jialiang Liang, Ipek Selcen, Haiyan Zheng, Dirk F. Moore, Patricia Casaccia

Advanced Science Research Center

The protein arginine methyl transferase PRMT5 is an enzyme expressed in oligodendrocyte lineage cells and responsible for the symmetric methylation of arginine residues on histone tails. Previous work from our laboratory identified PRMT5 as critical for myelination, due to its transcriptional regulation of genes involved in survival and early stages of differentiation. However, besides its nuclear localization, PRMT5 is found at high levels in the cytoplasm of several cell types, including oligodendrocyte progenitor cells (OPCs) and yet, its interacting partners in this lineage, remain elusive. By using mass spectrometry on protein eluates from extracts generated from primary oligodendrocyte lineage cells …

The Effects Of Nuclear Factor Erythroid 2 (Nfe2)-Related Factor 2 (Nrf2) Activation In Preclinical Models Of Peripheral Neuropathic Pain, Paramita Basu, Dayna L. Averitt, Camelia Maier, Arpita Basu

Kinesiology and Nutrition Sciences Faculty Research

Oxidative stress, resulting from an imbalance between the formation of damaging free radicals and availability of protective antioxidants, can contribute to peripheral neuropathic pain conditions. Reactive oxygen and nitrogen species, as well as products of the mitochondrial metabolism such as superoxide anions, hydrogen peroxide, and hydroxyl radicals, are common free radicals. Nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) is a transcription factor encoded by the NFE2L2 gene and is a member of the cap ‘n’ collar subfamily of basic region leucine zipper transcription factors. Under normal physiological conditions, Nrf2 remains bound to Kelch-like ECH-associated protein 1 in the cytoplasm …

Novel Strategies For Glutamate Clearance In The Glia-Deprived Synaptic Hub Of C. Elegans, Joyce Chan

Dissertations, Theses, and Capstone Projects

As the major excitatory neurotransmitter in the mammalian brain, Glutamate (Glu) is critical for normal neuronal physiology. Disruption in Glu clearance results in hyper-stimulation of glutamatergic circuits, potentially leading to excitotoxic neurodegeneration. The canonical model of brain connectivity describes glutamatergic synapses as well insulated and enveloped by glia. These glia express Glu Transporters (GluTs) which work to clear Glu following synaptic activity. However, critical areas of the brain such as the mammalian hippocampus display poor synaptic isolation, which may result in Glu spillover between adjacent synapses and subsequent loss of circuit specificity. How accurate signal transmission is achieved in these …

The Pathophysiological Mechanisms Of Alzheimer's Disease; Investigating Therapeutic Interventions For Disease Onset, Alexandra A. Sandberg

Electronic Theses and Dissertations

Alzheimer’s Disease is a multifarious disease that progressively affects more people as both the proportion of older adults in the population and life expectancy increase in both the United States and worldwide. This devastating disease is a result of rampant neuronal loss in the memory centers of the brain that robs the independence of those who are diagnosed and places a heavy burden on those who care for them. Traditionally speaking, research has focused on the hallmark pathology of amyloid plaques, targeting them to try and prevent disease onset. However, countless failures in clinical trials aimed at this said pathology …

The Effects Of Neuronal Growth Factors On Lps-Activated Schwann Cells, Caitlyn E. Henry, Peyton Kimmel, Angela Asirvatham Ph.D.

Student Research Poster Presentations 2022

Schwann cells (SCs) are the principal support cells of neurons in the peripheral nervous system, that both myelinate axons for the rapid conduction of electrical impulses as well as assist in axonal repair during nerve injury. During nerve injury, SCs secrete tumor necrosis factor alpha (TNF-α)^1,5,6 and other proinflammatory mediators^1,6, attracting macrophages to the site of injury to induce inflammation and clear myelin debris.^1,6 Once the debris is cleared, the neuron stimulates SC proliferation by secreting neuronal mitogens, such as heregulin^3,4, and an unknown factor that activates the cAMP pathway³, an important …

Simulation Of An Inflammatory Model Using Schwann Cells, Caitlyn Henry, Peyton Kimmel, Angela Asirvatham

Student Research Poster Presentations 2022

During peripheral nerve injury, the myelin surrounding the neuronal axons is damaged, initiating an inflammatory response to remove myelin debris. Once myelin debris is cleared, Schwann cells acquire a proliferating phenotype which allows them to grow and divide so that remyelination can occur. The neuron stimulates Schwann cell division by secreting growth factors, like heregulin, and an unknown growth factor that activates the cAMP pathway. Although the role of cAMP in axonal regeneration is well-known, not much has been explored about its function in Schwann cells during nerve injury and inflammation. To simulate an inflammatory environment, the S16 Schwann cell …