Neuroscience and Neurobiology Commons^™

Cellular-Based Brain Pathology In The Anterior Cingulate Cortex Of Males With Autism Spectrum Disorder, Jessica D. Crawford

Electronic Theses and Dissertations

Autism spectrum disorder (ASD) now affects 1 in 68 children in the United States. Disorders within this spectrum share hallmark deficits in verbal and nonverbal communication, repetitive behavior, and social interaction. The cause of ASD is still unknown. Even though hundreds of genetic abnormalities have been identified in ASD, these markers account for less than 1% of all ASD cases. Researchers continue to search for pathological markers common to all or most cases of ASD. The research presented in this dissertation used a novel combination of state-of-the-art methods to investigate brain pathology in ASD. Postmortem anterior cingulate cortex (ACC) from …

A Comprehensive Study Of The Effects Of Neurotoxins On Noradrenergic Phenotypes, Neuronal Responses And Potential Intervention By Antidepressants In Noradrenergic Cells, Yan Wang

Electronic Theses and Dissertations

It has been reported that locus coeruleus (LC) degeneration precedes the degeneration of other neurons in the brain in some neurodegenerative diseases like Alzheimer’s disease (AD) and Parkinson’s disease (PD). However, the precise mechanisms of neurodegeneration remain to be elucidated. N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) has been widely used as a noradrenergic neurotoxin in the development of AD and PD animal models for specific LC degeneration. However, the precise mechanism of action of DSP4 remains unclear. An increased systemic DNA damage caused by neurotoxin or oxidative stress has been found to be related to the pathogenic development of neurodegeneration. The process of neurodegeneration …

Functional Characterization Of The Arginine Vasotocin 4 Receptor (Vt4r) In Sensory Circumventricular Organs Of The Chicken Gallus Gallus, Nguiessan Alphonse Aman

Graduate Theses and Dissertations

Past studies have shown that the avian vasotocin 4 receptor (VT4R), homologous to the mammalian arginine vasopressin receptor 1a (V1aR/AVPR1A) is involved in immobilization stress. It was not known, however, whether the receptor is also associated with osmotic stress, and if so, what brain regions may be involved. Four treatment groups of chicks were used for the study. One group was subjected to 1h immobilization stress and two groups were administered intraperitoneal injection of 3 M NaCl or 0.15 M NaCl. One additional group served as controls. After 1 h, blood samples were taken for the determination of plasma levels …

Pathway-Specific Signaling And Its Impact On Fertility: A Focus On The Kisspeptin Receptor, Kiss1r, Maryse R. Ahow

Electronic Thesis and Dissertation Repository

Hypothalamic GnRH-releasing hormone (Gnrh) is the master regulator of the neuroendocrine reproductive axis and its secretion is regulated by many Gnrh neuronal-based signaling systems. Among these are Gα_q/11-coupled receptors and their ligands.In most cases examined to date, activation of these receptors lead to Gnrh neuronal membrane depolarization and Gnrh secretion. The most potent trigger of Gnrh secretion is kisspeptin (Kp), a ligand for the Kiss1r Gα_q/11-coupled receptor. Studies have shown that Kiss1r signaling is essential for attaining and maintaining fertility. We recently demonstrated that in addition to signaling via Gα_q/11, Kiss1r also couples to …

The Role Of The Rna-Binding Protein Rho Guanine Nucleotide Exchange Factor In The Cellular Stress Response, Kevin Wh Cheung

Electronic Thesis and Dissertation Repository

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease for which the pathological mechanism is heterogeneous and a cure has been elusive. Recent developments have linked specific proteins found in pathological neuronal cytoplasmic inclusions (NCIs) of ALS motor neurons to familial variants of the disease. These proteins, including TAR DNA-binding protein of 43 kDa (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS), and Rho guanine nucleotide exchange factor (RGNEF) share the common characteristic of being RNA-binding proteins that colocalize within NCIs. RGNEF is unique however in also possessing RhoA activation capacity, suggesting a role in the cell stress response. My thesis …

Characterization Of Human 82-Kda Choline Acetyltransferase Expression In A Newly Developed Transgenic Mouse Model, Silke M. Vanvaerenbergh

Electronic Thesis and Dissertation Repository

Expression of human 82-kDa choline acetyltransferase (ChAT) protein in nuclei of cultured neurons from Alzheimer’s disease model APP/PS1 transgenic mice results in a reduction in Aβ release, suggesting a protective role. This thesis characterizes the expression of human 82-kDa ChAT in 82-hChAT;NkCre transgenic mice by PCR-based examination of genomic DNA and localization of the protein in mice brains. First, I demonstrate in a cultured cell model that Cre recombinase-mediated excision of a floxed LacZ gene is necessary for human 82-kDa ChAT protein expression from pcCALL2:82-ChAT, the plasmid used to create founder transgenic mice. Second, I confirmed that human 82-kDa ChAT …

Synaptic Architecture Of The Acoustic Startle Response Pathway, Mahabba Smoka

Electronic Thesis and Dissertation Repository

The acoustic startle response (ASR) is mediated by a simple pathway which includes the giant neurons of the caudal pontine reticular nucleus (PnC). Habituation is theorized to occur via hyperpolarizing big potassium (BK) channels localized at glutamatergic terminals of auditory afferents in the PnC. Prepulse inhibition is suggested to be mediated by cholinergic innervation of PnC giant neurons, with possible glutamate and/or GABA co-release. Animals were injected with Fluorogold at C3/C4 to label a subpopulation of PnC giant neurons, and following a startle experiment, brainstems were processed for pCREB expression. Using their respective markers, BK channels, glutamatergic, GABAergic, and cholinergic …

Sox9 Conditional Knockdown Reduces Chondroitin Sulphate Proteoglycan Expression, Increases Neuroplasticity, And Improves Motor Function In A Mouse Model Of Spinal Cord Injury, William M. Mckillop

Electronic Thesis and Dissertation Repository

This thesis investigates the effect of Sox9 knockdown on anti-regenerative scar gene expression, neuroplasticity, and hind limb functional recovery following mouse spinal cord injury. We hypothesized that Sox9 knockdown would reduce expression of anti-regenerative chondroitin sulfate proteoglycans both at the lesion site and at sites distant to the injury, thus providing an avenue for increased neuroplasticity and locomotor recovery after spinal cord injury. The first chapter provides a general introduction to the biological problem of spinal cord injury. The development of the glial scar and expression of the anti-regenerative chondroitin sulfate proteoglycan extracellular matrix is introduced, and Sox9 is identified …

Neuromodulation Therapy Mitigates Heart Failure Induced Hippocampal Damage, Timothy P. Diperi

Undergraduate Honors Theses

Cardiovascular disease (CVD) is the leading cause of death in the United States. Nearly half of the people diagnosed with heart failure (HF) die within 5 years of diagnosis. Brain abnormalities secondary to CVD have been observed in many discrete regions, including the hippocampus. Nearly 25% of patients with CVD also have major depressive disorder (MDD), and hippocampal dysfunction is a characteristic of both diseases. In this study, the hippocampus and an area of the hippocampal formation, the dentate gyrus (DG), were studied in a canine model of HF. Using this canine HF model previously, we have determined that myocardial …

Propagation Of Oligomeric Α-Synuclein And Amyloid-Β: Implications For Parkinson's And Alzheimer's Diseases, Matthew Stephen Planchard

Master's Theses

The aggregation of amyloidogenic proteins is a critical event in the pathology of a variety of neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). The proteins α-synuclein (αS) and amyloid-β (Aβ) are involved in the formation of amyloid lesions observed in PD and AD, respectively. Both PD and AD exhibit a significant amount of co-pathology in clinical settings, and the αS and Aβ proteins have been shown to interact in vitro. Recent experimental consensus has shown oligomeric species to be significant, if not primary, sources of toxicity in these diseases. …

The Molecular Components Of Estrogen Receptor Beta (Erβ) Signaling In Neuronal Sytems, Natasha Mott

Dissertations

With increasing life expectancy, women are now living upwards of 50 years without circulating estrogens, therefore, it is essential to investigate how the brain is changed by estrogen deprivation and also how aging influences these changes. The Women's Health Initiative (WHI) study spurred rigorous debate regarding estrogen therapy for postmenopausal women due to dichotomous effects of estrogens in menopausal and post-menopausal women. Meta-analyses of the WHI study revealed that after circulating estrogens are depleted for many years re-exposure may cause aberrant, negative health effects, indicating that there is an age-related `switch' in estrogen signaling around menopause. These age-related effects of …

Rho Gtpases In Neuronal Apoptosis And Neurodegeneration, Trisha Stankiewicz

Electronic Theses and Dissertations

Several studies have identified Rho family GTPases (i.e. Rho, Rac, Cdc42) as mediators of diverse critical cellular processes, such as actin cytoskeleton remodeling, gene transcription, cell-cell adhesion, and cell cycle progression. However, more recent data highlight an essential role for Rho GTPases as regulators of neuronal morphology and neuronal survival. In particular, Rac GTPase generally induces neurite outgrowth and promotes neuronal survival while Rho GTPase typically provokes neurite retraction and induces neuronal apoptosis. However, the precise signaling pathways that regulate neuronal survival downstream of Rho GTPases and the potential involvement of dysregulated activity of Rho GTPases as a causative factor …

An Environmental Toxic Model Of Parkinson's Disease: The Fruit Fly, Jennene Lyda

Graduate Student Theses, Dissertations, & Professional Papers

Parkinson’s disease (PD) is the second most common neurodegenerative disorder with no known specific cause; although genetic risk factors and/or environmental exposure are thought to be involved. The etiology of PD is currently unknown, although the combination of non-genetic components such as environmental exposures, the accumulation of exposure, and gene-environment interactions are thought to play a major role. However, despite this knowledge it is important to develop better models that parallel PD pathophysiology to further understand the mechanisms underlying dopaminergic neuron (DaN) damage. The use of mammalian models to study the degenerative processes in PD has been the most common …

Calpain 5: A Non-Classical Calpain Highly Expressed In The Cns And Localized To Mitochondria And Nuclear Pml Bodies, Ranjana Singh

Theses and Dissertations--Neuroscience

Calpain 5 (CAPN5) is a non-classical member of the calpain family. It lacks the EF-hand motif characteristic of the classical calpains, calpain 1 and 2, but retains catalytic and Ca²⁺ binding non EF domains. Tra-3, an ortholog of CAPN5, is involved in necrotic cell death in C.elegans; although specific role of CAPN5 has not been investigated in the mammalian CNS. I compared relative mRNA levels of calpains in rat CNS, which revealed that CAPN5 is the second most highly expressed calpain. We examined relative levels of CAPN5 from late embryonic day 18 to postnatal day 90 and …

Flavonoids With Novel Nicotinic Activity As Potential Pharmacotherapies To Treat Ethanol-Induced Neurotoxicity, Joseph A. Lutz

Theses and Dissertations--Pharmacy

Ethanol causes neurotoxicity via several mechanisms at different points in the cycle of dependence, including neuroinflammation and oxidative stress during ethanol exposure as well as excitotoxicity during ethanol withdrawal. The primary therapeutic implication is that ethanol-induced neurotoxicity requires multifunctional pharmacotherapies which reduce all mechanisms. Using an innovative pharmacological high throughput screening method on a large plant extract library we discovered flavonoids with alpha7 nicotinic acetylcholine receptor (nAChR) activity. In addition to their well-known anti-inflammatory and antioxidant properties, this novel activity means they can potentially reduce excitotoxicity and therefore makes them ideal for inhibition of ethanol-induced neurotoxicity. Rhamnetin, the candidate compound, …

Characterizing A Novel Monoclonal Ampa Receptor 1/2/3 Antibody In The Hippocampus And Prefrontal Cortex Of Rat, Monkey, And Human, Sebastian Aguiar

Pitzer Senior Theses

The excitatory, ionotropic glutamatergic AMPA receptor is the most common membrane-bound receptor in the central nervous system. AMPARs and the NMDA receptors are central to synaptic plasticity, memory, and mechanisms of neurodegeneration. The AMPAR is an obligate heterotetramer, composed of subunits GluA1-4. Subunit permutation determines ion conductance, trafficking and other functional characteristics. Few available antibodies are subunit-specific, disabling researchers from accurately visualizing differential AMPAR subunit distribution in the nervous system. This study sought to visualize a novel monoclonal GluA1/2/3 antibody with functional avidity for three of four receptor subunits and to characterize the ultrastructural localization of these receptors using confocal …

Dopaminergic And Activity-Dependent Modulation Of Mechanosensory Responses In Drosophila Melanogaster Larvae, Josh S. Titlow

Theses and Dissertations--Biology

A central theme of this dissertation is nervous system plasticity. Activity-dependent plasticity and dopaminergic modulation are two processes by which neural circuits adapt their function to developmental and environmental changes. These processes are involved in basic cognitive functions and can contribute to neurological disorder. An important goal in modern neurobiology is understanding how genotypic variation influences plasticity, and leveraging the quantitative genetics resources in model organisms is a valuable component of this endeavor. To this end I investigated activity-dependent plasticity and dopaminergic modulation in Drosophila melanogaster larvae using neurobiological and genetic approaches.

Larval mechanosensory behavior is described in Chapter 2. …

Characterization Of The Transporter Protein Sodium-Potassium Adenosine Triphosphatase In The Myelin Membrane, Dara E C Schaefer

Theses and Dissertations (Comprehensive)

Sodium-potassium adenosine triphosphatase (Na⁺/K⁺-ATPase) is an integral membrane protein with known involvement in the maintenance of resting membrane potentials, nutrient uptake, cellular signal transduction, and cell-cell adhesion. The functional enzyme contains a catalytic alpha subunit and a glycosylated beta subunit, of which three isoforms of each are known to exist in the central nervous system (CNS). Altered expression and/or activity of Na⁺/K⁺-ATPase subunit isoforms has been previously implicated in the pathophysiology of several neurological disorders. This study characterized Na⁺/K⁺-ATPase expression and distribution in the myelin membrane, identified its …