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Divergence In Neuronal Calcium Dysregulation In Brain Aging And Animal Models Of Ad, Adam Ghoweri Jan 2020

Divergence In Neuronal Calcium Dysregulation In Brain Aging And Animal Models Of Ad, Adam Ghoweri

Theses and Dissertations--Pharmacology and Nutritional Sciences

Neuronal calcium dysregulation first garnered attention during the mid-1980’s as a key factor in brain aging, which led to the formulation of the Ca2+ hypothesis of brain aging and dementia. Indeed, many Ca2+-dependent cellular processes that change with age, including an increase in the afterhyperpolarization, a decrease in long-term potentiation, an increased susceptibility to long-term depression, and a reduction in short-term synaptic plasticity, have been identified. It was later determined that increased intracellular Ca2+ with age was due to increased Ca2+ channel density, elevated release from intracellular Ca2+ stores, and decreased Ca2+ buffering …


Pharmaceutical And Natural (Exercise) Mechanisms To Mitigate The Negative Impact Of Ptsd And Chronic Stress On Synaptic Plasticity And Memory, Roxanne M. Miller Nov 2017

Pharmaceutical And Natural (Exercise) Mechanisms To Mitigate The Negative Impact Of Ptsd And Chronic Stress On Synaptic Plasticity And Memory, Roxanne M. Miller

Theses and Dissertations

Synapses can be altered due to experiences in a process called synaptic plasticity, which causes memory formations. Synapses can be strengthened through methods known as long-term potentiation (LTP) or weakened through long-term depression (LTD). Stresses can cause changes by altering synapses through either LTP or LTD. Rats were used to study the effects of post-traumatic stress disorder (PTSD)-like symptoms and a prophylactic treatment using pharmaceuticals. The first model used was the single prolonged stress (SPS) with two weeks of chronic light, which was not as effective for causing changes in synaptic plasticity. The second model, seven days of social defeat …


Pharmaceutical And Natural (Exercise) Mechanisms To Mitigate The Negative Impact Of Ptsd And Chronic Stress On Synaptic Plasticity And Memory, Roxanne M. Miller Nov 2017

Pharmaceutical And Natural (Exercise) Mechanisms To Mitigate The Negative Impact Of Ptsd And Chronic Stress On Synaptic Plasticity And Memory, Roxanne M. Miller

Theses and Dissertations

Synapses can be altered due to experiences in a process called synaptic plasticity, which causes memory formations. Synapses can be strengthened through methods known as long-term potentiation (LTP) or weakened through long-term depression (LTD). Stresses can cause changes by altering synapses through either LTP or LTD. Rats were used to study the effects of post-traumatic stress disorder (PTSD)-like symptoms and a prophylactic treatment using pharmaceuticals. The first model used was the single prolonged stress (SPS) with two weeks of chronic light, which was not as effective for causing changes in synaptic plasticity. The second model, seven days of social defeat …


Quantification Of Brain-Region Specific Alterations In Insulin-Like Growth Factor-1 Expression During Developmental Hypothyroidism, Cari Lee Graber-Feesl Jan 2017

Quantification Of Brain-Region Specific Alterations In Insulin-Like Growth Factor-1 Expression During Developmental Hypothyroidism, Cari Lee Graber-Feesl

All Graduate Theses, Dissertations, and Other Capstone Projects

Insufficient thyroid hormone (TH) during development results in permanent neurological deficits. These deficits are the result of perturbed TH-mediated brain development. Interestingly, insufficient insulin-like growth factor 1 (Igf-1) during development results in neurological deficits that are similar to those reported for developmental hypothyroidism. This observation suggests that deficits associated with low TH during development may be the result of altered Igf-1 expression in the developing brain. To test this, timed-pregnant mice were treated with thyroid gland inhibitors from gestational day 16 (GD16) until postnatal day 21 (P21) to induce a hypothyroid state. A parallel set of untreated timed-pregnant mice were …


Repeated Closed Head Injury In Mice Results In Sustained Motor And Memory Deficits And Chronic Cellular Changes, Amanda Nicholle Bolton Hall, Binoy Joseph, Jennifer M. Brelsfoard, Kathryn E. Saatman Jul 2016

Repeated Closed Head Injury In Mice Results In Sustained Motor And Memory Deficits And Chronic Cellular Changes, Amanda Nicholle Bolton Hall, Binoy Joseph, Jennifer M. Brelsfoard, Kathryn E. Saatman

Spinal Cord and Brain Injury Research Center Faculty Publications

Millions of mild traumatic brain injuries (TBIs) occur every year in the United States, with many people subject to multiple head injuries that can lead to chronic behavioral dysfunction. We previously reported that mild TBI induced using closed head injuries (CHI) repeated at 24h intervals produced more acute neuron death and glial reactivity than a single CHI, and increasing the length of time between injuries to 48h reduced the cumulative acute effects of repeated CHI. To determine whether repeated CHI is associated with behavioral dysfunction or persistent cellular damage, mice receiving either five CHI at 24h intervals, five CHI at …


A Semi-Automated Algorithm For Segmenting The Hippocampus In Patient And Control Populations, Nathan Mckay Muncy Jun 2016

A Semi-Automated Algorithm For Segmenting The Hippocampus In Patient And Control Populations, Nathan Mckay Muncy

Theses and Dissertations

Calculating hippocampal volume from Magnetic Resonance (MR) images is an essential task in many studies of neurocognition in healthy and diseased populations. The `gold standard' method involves hand tracing, which is accurate but laborious, requiring expertly trained researchers and significant amounts of time. As such, segmenting large datasets with the standard method is impractical. Current automated pipelines are inaccurate at hippocampal demarcation and volumetry. We developed a semi-automated hippocampal segmentation pipeline based on the Advanced Normalization Tools (ANTs) suite of programs to segment the hippocampus. We applied the semi-automated segmentation pipeline to 70 participant scans (26 female) from groups that …


An Evaluation Of The Influences Of Extra-Hippocampal Processes On Pattern Separation, Malia L. Anderson Apr 2016

An Evaluation Of The Influences Of Extra-Hippocampal Processes On Pattern Separation, Malia L. Anderson

Theses and Dissertations

Long-term declarative memory depends on pattern separation, which reduces the degree of overlap between similar representations, to maintain memory specificity, and on pattern completion, which occurs when a degraded cue is used to retrieve a previously stored memory. Previous studies aimed at evaluating the underlying neuronal substrates of these computational processes have used a mnemonic discrimination paradigm and fMRI to focus on the hippocampus, to the exclusion of cortical processing. We aim to investigate the influences extra-hippocampal processes have on pattern separation in the following two studies. Study 1. Computational models of pattern completion suggest it occurs cortically and results …


A Neuroimaging Investigation Of The Effects Of Age And Sleep On Pattern Separation, Christopher Robert Doxey Mar 2016

A Neuroimaging Investigation Of The Effects Of Age And Sleep On Pattern Separation, Christopher Robert Doxey

Theses and Dissertations

Effective memory representations must be specific to prevent interference between episodes that may overlap in terms of place, time, or items present. Pattern separation, a computational process performed by the hippocampus overcomes this interference by establishing non-overlapping memory representations. This project explores pattern separation and how it is impacted by age and sleep. Experiment 1. Structures of the medial temporal lobe (MTL) are known to be involved in declarative memory processes. However, little is known about how age-related changes in MTL structures, white matter integrity, and functional connectivity affect pattern separation processes in the MTL. In the present study, we …


Genetic And Acute Cpeb1 Depletion Ameliorate Fragile X Pathophysiology, Tsuyoshi Udagawa, Natalie Farny, Mira Jakovcevski, Hanoch Kaphzan, Juan Alarcon, Shobha Anilkumar, Maria Ivshina, Jessica Hurt, Kentaro Nagaoka, Vijayalaxmi Nalavadi, Lori Lorenz, Gary Bassell, Schahram Akbarian, Sumantra Chattarji, Eric Klann, Joel Richter Dec 2015

Genetic And Acute Cpeb1 Depletion Ameliorate Fragile X Pathophysiology, Tsuyoshi Udagawa, Natalie Farny, Mira Jakovcevski, Hanoch Kaphzan, Juan Alarcon, Shobha Anilkumar, Maria Ivshina, Jessica Hurt, Kentaro Nagaoka, Vijayalaxmi Nalavadi, Lori Lorenz, Gary Bassell, Schahram Akbarian, Sumantra Chattarji, Eric Klann, Joel Richter

Natalie G. Farny

Fragile X syndrome (FXS), the most common cause of inherited mental retardation and autism, is caused by transcriptional silencing of FMR1, which encodes the translational repressor fragile X mental retardation protein (FMRP). FMRP and cytoplasmic polyadenylation element-binding protein (CPEB), an activator of translation, are present in neuronal dendrites, are predicted to bind many of the same mRNAs and may mediate a translational homeostasis that, when imbalanced, results in FXS. Consistent with this possibility, Fmr1(-/y); Cpeb1(-/-) double-knockout mice displayed amelioration of biochemical, morphological, electrophysiological and behavioral phenotypes associated with FXS. Acute depletion of CPEB1 in the hippocampus of adult Fmr1(-/y) mice …


Effects Of Rapamycin Treatment On Neurogenesis And Synaptic Reorganization In The Dentate Gyrus After Controlled Cortical Impact Injury In Mice, Corwin R. Butler, Jeffery A. Boychuk, Bret N. Smith Nov 2015

Effects Of Rapamycin Treatment On Neurogenesis And Synaptic Reorganization In The Dentate Gyrus After Controlled Cortical Impact Injury In Mice, Corwin R. Butler, Jeffery A. Boychuk, Bret N. Smith

Physiology Faculty Publications

Post-traumatic epilepsy (PTE) is one consequence of traumatic brain injury (TBI). A prominent cell signaling pathway activated in animal models of both TBI and epilepsy is the mammalian target of rapamycin (mTOR). Inhibition of mTOR with rapamycin has shown promise as a potential modulator of epileptogenesis in several animal models of epilepsy, but cellular mechanisms linking mTOR expression and epileptogenesis are unclear. In this study, the role of mTOR in modifying functional hippocampal circuit reorganization after focal TBI induced by controlled cortical impact (CCI) was investigated. Rapamycin (3 or 10 mg/kg), an inhibitor of mTOR signaling, was administered by intraperitoneal …


Regulation Of Micrornas By 17Β-Estradiol In The Aging Female Brain, Yathindar Satya Giffin-Rao Jan 2015

Regulation Of Micrornas By 17Β-Estradiol In The Aging Female Brain, Yathindar Satya Giffin-Rao

Dissertations

Hormone Therapy (HT) is used to increase the 17β-estradiol (E2) levels in women who are going through the menopausal transition to alleviate the negative symptoms associated with menopause and decrease the risk of chronic diseases. Clinical and basic science research had previously shown that HT provided protection from cognitive decline and reduced the risk of dementia. However the Women's Health Initiative (WHI) clinical trial demonstrated that HT had no beneficial effects for cognitive decline and, in some cases increased the risk of dementia in post-menopausal women. However, further analysis of WHI data showed that when HT was given to women …


Effect Of Long-Term Physical Exercise On Blood Pressure In African Americans, Taunjah P. Bell, Katharine A. Mcintyre, Rosamary Hadley Jul 2014

Effect Of Long-Term Physical Exercise On Blood Pressure In African Americans, Taunjah P. Bell, Katharine A. Mcintyre, Rosamary Hadley

International Journal of Exercise Science

International Journal of Exercise Science 7(3) : 186-193, 2014. Long-term physical exercise has been shown to noticeably reduce blood pressure (BP) and remarkably attenuate symptoms of hypertension. It is believed that physical exercise induces these beneficial effects by increasing the blood supply to the brain, enhancing the release of growth factors from skeletal muscles into the bloodstream, facilitating neurogenesis, stimulating angiogenesis, and influencing endothelial cell proliferation and subsequent endothelial cell membrane permeability. Previous findings also revealed that physical exercise significantly elevates brain-derived neurotrophic factor (BDNF) concentrations which appear to increase dramatically in BP-sensing neurons during hypertension. Elevating BDNF levels is …


Loss Of Dendritic Inhibition In The Hippocampus After Repeated Early-Life Hyperthermic Seizures In Rats., Richard Boyce, L Stan Leung Jan 2013

Loss Of Dendritic Inhibition In The Hippocampus After Repeated Early-Life Hyperthermic Seizures In Rats., Richard Boyce, L Stan Leung

Physiology and Pharmacology Publications

Seizures are relatively common in children and are a risk factor for subsequent temporal lobe epilepsy. To investigate whether early-life seizures themselves are detrimental to the proper function of the adult brain, we studied whether dendritic excitation and inhibition in the hippocampus of adult rats were altered after hyperthermia-induced seizures in immature rats. In particular, we hypothesized that apical dendritic inhibition in hippocampal CA1 pyramidal cells would be disrupted following hyperthermia-induced seizures in early life. Seizure rats were given three hyperthermia-induced seizures per day for three days from postnatal day (PND) 13 to 15; control rats were handled similarly but …


Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction In A Mouse Model That Exhibits Age-Dependent Progression Of Alzheimer's Disease-Related Pathology, Adam D. Bachstetter, Christopher M. Norris, Pradoldej Sompol, Donna M. Wilcock, Danielle Goulding, Janna H. Neltner, Daret St. Clair, D. Martin Watterson, Linda J. Van Eldik Jul 2012

Early Stage Drug Treatment That Normalizes Proinflammatory Cytokine Production Attenuates Synaptic Dysfunction In A Mouse Model That Exhibits Age-Dependent Progression Of Alzheimer's Disease-Related Pathology, Adam D. Bachstetter, Christopher M. Norris, Pradoldej Sompol, Donna M. Wilcock, Danielle Goulding, Janna H. Neltner, Daret St. Clair, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

Overproduction of proinflammatory cytokines in the CNS has been implicated as a key contributor to pathophysiology progression in Alzheimer's disease (AD), and extensive studies with animal models have shown that selective suppression of excessive glial proinflammatory cytokines can improve neurologic outcomes. The prior art, therefore, raises the logical postulation that intervention with drugs targeting dysregulated glial proinflammatory cytokine production might be effective disease-modifying therapeutics if used in the appropriate biological time window. To test the hypothesis that early stage intervention with such drugs might be therapeutically beneficial, we examined the impact of intervention with MW01-2-151SRM (MW-151), an experimental therapeutic that …


Expression And Function Of Alpha3 And Beta2 Neuronal Nicotinic Acetylcholine Receptor Subunits In Hek-293 Cells, Nathan W. Steinhafel Dec 2006

Expression And Function Of Alpha3 And Beta2 Neuronal Nicotinic Acetylcholine Receptor Subunits In Hek-293 Cells, Nathan W. Steinhafel

Theses and Dissertations

Single-cell real-time quantitative RT-PCR was used to characterize the mRNA expression of rat neuronal nicotinic acetylcholine receptor (nAChR) subunits α3 and β2 in CA1 hippocampus stratum radiatum and stratum oriens interneurons. α3β2 co-expression was detected in 43% of interneurons analyzed. The nAChR subtype α3β2 was transiently expressed in cells derived from the human embryonic kidney cell line 293 at mRNA levels found in the CA1. The functional properties of α3β2 in HEK-293 cells were characterized by whole-cell patch clamping using acetylcholine (ACh) as an agonist. The kinetics of α3β2 channels were further analyzed by altering the level of α3 DNA …