Molecular and Cellular Neuroscience Commons^™

The Impact Of Diabetes On Neurovascular Integrity: A Special Focus On Pericytes And Endothelin-1, Mia Edgerton

MUSC Theses and Dissertations

Diabetes increases the risk of stroke and Vascular Contributions to Cognitive Impairment and Dementia (VCID). Diabetes also dysregulates the endothelin (ET) system. ET-1-mediated constriction of brain microvascular pericytes (BMVPCs) has been shown to contribute to brain hypoperfusion. However, there is a loss of BMVPCs in VCID, but underlying mechanisms of pericyte degeneration are poorly studied. ETA receptor activation can instigate phenotypical changes and cellular senescence in endothelial cells. . There is also emerging evidence that ETB receptor agonism improves outcomes in patients with cerebral ischemic stroke, but long-term effects, especially in diabetes, are unknown. Therefore, this study aimed to determine …

Influences Of Sex, Alcohol, And Stress On Conditioned Fear Responses, Heyam K. Mayberry

MUSC Theses and Dissertations

Learned fear responses are acquired through the identification and association of threatening stimuli with aversive outcomes. Fear responding and the proper maintenance of defensive behaviors is integral to survival. However, without the homeostasis of such systems, fear responses can become maladaptive and lead to dysregulated behavioral responding. Psychological conditions such as alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) often lead to impairments in fear learning, deficits in fear memory, and heightened fear responses. While there are clear sex differences in the prevalence of both AUD and PTSD, development of either disorder increases the risk for comorbid AUD/PTSD, leading …

Complement Propagates Visual System Pathology After Traumatic Brain Injury, Davis Marchant Borucki

MUSC Theses and Dissertations

Background: Traumatic brain injury is associated with the development of visual system disorders, including deficits in visual acuity. Visual deficits can present with delay and worsen over time, suggesting that ongoing neuroinflammatory changes contribute to their development and progression. Complement activation is strongly associated with the neuroinflammatory response after TBI and has been shown to contribute to neuronal and synaptic loss. However, the contributions of complement activation after TBI to vision loss remains unclear.

Methods: We employed an open skull controlled cortical impact model of traumatic brain injury in adult male mice to study how TBI affects vision. Animals were …

The Role Of Complement In Stroke And Traumatic Brain Injury, Christine Couch

MUSC Theses and Dissertations

Brain and neural injury are a non-specific disease category that includes traumatic brain injury (TBI) and stroke. Both TBI and stroke are common, costly, and leading causes of severe disability in adults. Both stroke and TBI are responsible for substantial disability in working age adults, with stroke being the second leading cause of death worldwide [1] and TBI a major cause of disability in people younger than their 40's [2]. The immune response after brain injury is multifactorial and involves both local and systemic events at the cellular and molecular level. The complement system is a component of both the …

Cell-Type Specific Extracellular Matrix Signaling In The Opioid-Addicted Synapse, Vivian C. Chioma

MUSC Theses and Dissertations

To date, heroin abuse is a leading cause of drug overdose-related deaths in the United States, highlighting a need for further research elucidating effects of maladaptive neuroadaptations following prolonged heroin use. Activation of the tetrapartite synapse in nucleus accumbens core (NAcore), which comprises of pre- and post-synapse, astrocytic processes, and surrounding extracellular matrix (ECM), has been linked to increased relapse vulnerability. Specifically, degradation of ECM by activated matrix metalloproteinases (MMPs) is involved in extracellular synaptic remodeling both constitutively and transiently in extinguished and drug seeking conditions, respectively. Although increases in MMP-2,9 fluorescence can be localized to soma and dendritic processes …

Signals From The 4th Dimension: Role Of Extracellular Matrix Signaling In Synaptic Plasticity Mediating Addiction, Alexander C. W. Smith

MUSC Theses and Dissertations

Chronic cocaine abuse causes maladaptive neuroadaptations that underlie vulnerability to relapse, even after protracted abstinence. A great deal of work has examined mechanisms of neuroplasticity by which these occur. However, the majority of experimentation has focused on intracellular signaling cascades, while the extracellular compartment has been largely ignored. In the past decade, work has emerged in the learning and memory literature that indicates that extracellular matrix remodeling and signaling is required for adaptive forms of neuroplasticity (e.g. learning and memory), although it has not been thoroughly examined in models of maladaptive neuroplasticity. Throughout this dissertation a drug self-administration, extinction and …

Glutamatergic Neurotransmission In The Prefrontal Cortex Mediates The Suppressive Effect Of Intra-Pfc Infusion Of Bdnf On Cocaine-Seeking, Bok Soon Go

MUSC Theses and Dissertations

Infusion of BDNF into the dorsomedial prefrontal cortex (dmPFC) immediately after the last session of cocaine self-administration prevents cocaine-mediated malfunction of synaptic modulation in the dmPFC that mediates relapse to cocaine-seeking through both GluN2A subunit-containing NMDA receptors and GluN2B subunit-containing NMDA receptors (NMDARS). Intra-dmPFC BDNF is known to suppress cocaine-seeking by normalization of cocaine self-administration- induced disturbance of glutamatergic transmission in the nucleus accumbens (NAc) and by prevention of the cocaine self-administration-induced decrease in extracellular signal-regulated kinase (ERK) activity in the dmPFC through activation of tyrosine receptor kinase B (TrkB). Neuronal activity is required for BDNF-induced ERK activation and the …

Phosphodiesterase Inhibition And Adenosine A2b Receptor Signaling In Mitochondrial Function: Pharmacology And Toxicology Of 3-Isobutyl 1-Methylxanthine (Ibmx) In The 661w Retina-Derived Cell Line, Anthony Presley Leonard

MUSC Theses and Dissertations

3-isobutyl 1-methylxanthine (IBMX) is a commonly used inhibitor of cyclic nucleotide phosphodiesterases (PDE) and G protein coupled adenosine receptors. Administration of IBMX to retina photoreceptor-derived 661w cell line results in decreased mitochondrial respiration followed by cell death, mimicking phenomena observed in inherited retina neurodegeneration in humans and animals and thus suggesting their use as a cell-based model of retina degeneration. In this dissertation, the temporal relationship between pathways altered by IBMX and how these pathways affect mitochondrial physiology are evaluated. These studies utilize a novel high content microscopic method for simultaneously measuring mitochondrial morphology and membrane potential in living cultured …