Medicine and Health Sciences Commons^™

Memory-Based Viewing: A Potential Marker Of Pathological Aging, Jenna Blujus

Theses and Dissertations

Markers of cognitive impairment are needed to distinguish normal from pathological aging prior to the onset of clinical symptomology to improve Alzheimer’s disease (AD) treatment or prevention efforts. AD pathology is believed to develop years or even decades prior to diagnosis in medial temporal lobe subregions that provide input to the hippocampus (Braak & Braak, 1991), disrupting the ability of the hippocampus to bind individual elements of an experience to form cohesive memory representations. Eye movement behavior is a sensitive index of learning and effects of memory on eye movements have been shown to emerge rapidly (within 500-750ms of stimuli …

Memory-Based Viewing: A Potential Marker Of Pathological Aging, Jenna Blujus

Theses and Dissertations

Markers of cognitive impairment are needed to distinguish normal from pathological aging prior to the onset of clinical symptomology to improve Alzheimer’s disease (AD) treatment or prevention efforts. AD pathology is believed to develop years or even decades prior to diagnosis in medial temporal lobe subregions that provide input to the hippocampus (Braak & Braak, 1991), disrupting the ability of the hippocampus to bind individual elements of an experience to form cohesive memory representations. Eye movement behavior is a sensitive index of learning and effects of memory on eye movements have been shown to emerge rapidly (within 500-750ms of stimuli …

The Effects Of Notch Signaling On Functional Recovery Following Traumatic Brain Injury, Jyoti Lodha

Theses and Dissertations

2.5 million people sustain a traumatic brain injury (TBI) annually in the United States. Although there is potential for functional recovery following TBI, there is no definitive treatment to improve recovery after TBI. Our lab has shown that TBI enhances an endogenous neurogenic response in the subventricular zone and hippocampus. TBI-induced neural stem cells (NSCs) can integrate into regions such as the hippocampus and olfactory bulb. Although the mechanism behind TBI-enhanced neurogenesis remains unknown, the Notch signaling pathway has been implicated as a regulator in the maintenance and survival of NSCs.

This thesis explores the effects of Notch pathway manipulation …

Connecting The Dots: Investigating The Effects Of Trans-Synaptic Tau Transmission In The Hippocampus, Michael Bamisile

Theses and Dissertations

Tauopathy, which results from the oligomerization of misfolded tau protein in neurons, is a feature present in a number of neurodegenerative diseases and a hallmark of Alzheimer’s Disease (AD). Tau is an important phosphoprotein that regulates the assembly of microtubules, but tauopathy can occur when tau becomes hyperphosphorylated. Phosphorylation prevents tau from binding to tubulin, which results in cytosolic accumulation of tau and eventual oligomerization. This abnormal accumulation of tau leads to the spreading of hyperphosphorylated tau to downstream synaptically connected neurons through an unknown mechanism. In AD, the hippocampus is one of the first brain structures to be affected …

The Identification Of The Direct And Indirect Pathways Through Which Leptin Facilitates Synaptic Plasticity In The Hippocampus, Catherine Van Doorn

Theses and Dissertations

Leptin, a peptide synthesized by adipocytes in the periphery, has been shown to play significant roles in feeding and energy expenditure mediated by the hypothalamus. Growing evidence supports the role of leptin in influencing synaptic plasticity in the hippocampus in that leptin dose-dependently enhances LTP, alters morphology and neurogenesis, facilitates spatial learning and memory, as well as memory retention. Models of leptin deficiency and resistance have further supported the importance of leptin in synaptic plasticity by exhibiting deficits in electrophysiological, morphological and behavioral tests that are improved after leptin restoration. The effects of leptin when applied directly into the hippocampus …

Status Epilepticus Induced Alterations In Hippocampal Anatomy And Neurotransmission, Denise K. Grosenbaugh

Theses and Dissertations

Status epilepticus (SE) is a life-threatening neurologic emergency occurring when the brain is in an unrelenting state of seizure activity. Approximately 40% of people who encounter a single event of SE go on to develop epilepsy, characterized by spontaneously occurring seizures. While the exact mechanisms underlying seizure origin are not understood, at a fundamental level seizures initiate due to an imbalance between inhibitory and excitatory neurotransmission. We explored the impact of SE and the development of epilepsy on GABAA receptor mediated inhibitory neurotransmission and kainate receptor (KAR) mediated excitatory neurotransmission.

Stiripentol (STP), a positive allosteric modulator of the GABAA receptor, …

The Effect Of Minocycline Treatment On Cell Proliferation And Neurogenesis In The Hippocampus In Young And Aged Brains Following Traumatic Brain Injury, Ashley Harvin

Theses and Dissertations

Following traumatic brain injury, there is an enhanced cell proliferative and neurogenic response in the young adult hippocampus, which may be associated with innate cognitive recovery. However, in the aged brain, an increased level of inflammatory cell responses was observed following injury concomitant to decreased hippocampal neurogenesis and cognitive recovery in the aging population. This suggests that excessive inflammation produced in the injured aging brain has a detrimental effect on neurogenesis and cognitive function. In this study, we examined the effect of anti-inflammatory treatment with minocycline on cell proliferation and generation of new neurons in the dentate gyrus (DG) of …

The Effects Of Bfgf Treatment In The Aged Brain Following Traumatic Brain Injury, Michael Zeigler

Theses and Dissertations

The mature mammalian brain continually generates new neurons in the subventricular zone and hippocampus throughout life. Adult neurogenesis in the hippocampus is associated with hippocampal-dependent learning and memory function. During aging, this endogenous neurogenic potential is reduced which is accompanied by decreased cognitive function seen in the aging population. We have previously found that the injured adult brain shows heightened levels of endogenous neurogenesis and this response is associated with innate cognitive recovery. We have also found that basic fibroblast growth factor (bFGF), a potent neurotrophic polypeptide, can enhance injury-induced hippocampal neurogenesis and improve cognitive recovery following TBI. In this …

The Expression And Function Of Phosphacan/Rptpβ In Adaptive Synaptogenesis After Traumatic Brain Injury, Janna Harris

Theses and Dissertations

Traumatic brain injury (TBI) affects 1.5 million Americans annually and is a major health concern. Increasing evidence suggests that the brain extracellular environment regulates plasticity and synaptic recovery following TBI. Here we have focused on phosphacan/RPTPβ, an alternatively spliced group of chondroitin sulfate proteoglycans which are prominent within the mature brain extracellular matrix (ECM). Previous studies show that phosphacan/RPTPβ influences neuronal migration, adhesion, neurite outgrowth, and morphogenesis. However, our understanding of how these important ECM components are involved in recovery from brain trauma remains unclear. In the present study, we used unilateral entorhinal cortex lesion (UEC), a model which induces …