Anatomy Commons^™

Using Functionalized Benzylidene Oxindoles To Determine An Improved Monoamine Oxidase-B Inhibitor As A Therapeutic Agent For Parkinson's Disease, Christine Morgan Kinstedt

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With the intent to create an optimized monoamine oxidase-B (MAO-B) inhibitor, researchers in this investigation synthesized derivatives of the benzylidene oxindole scaffold in order to determine a lead molecule for further drug development. Previous work in this laboratory group evaluated a similar scaffold, the chalcone structural unit. As this class of compounds was determined to possess the ability to permeate the blood brain barrier (BBB) and to act as potent MAO-B inhibitors, it was posited that scaffold hopping from this previously studied molecular skeleton to benzylidene oxindoles would provide analogous results. Benzylidene oxindoles are readily synthesized via the Claisen-Schmidt condensation …

Characterization Of Inhbb, Heatr5a, & Cyp2s1 Expression In Dorsal Root Ganglia By In-Situ Hybridization, Joshua D. Krech

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Multiple studies have shown that gene expression changes occur in sensory neurons after peripheral nerve injury (PNI). These expression changes include many genes that are turned on specifically in response to injury, but much less is know about expression changes in stable genetic markers of particular sensory neuron populations. This study characterized the expression of three markers of proprioceptive neurons Inhbb, Heatr5a, Cyp2s1 in lumbar dorsal root ganglion (DRG) neurons in intact animals and after PNI. To perform these experiments, we subcloned segments of the coding sequences of these genes and generated DIG-labeled riboprobes. Control experiments demonstrated the validity of …

Using Fmri Bold Imaging To Motion-Correct Associated, Simultaneously Imaged Pet Data, Joseph M. Williamitis

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Because magnetic resonance (MR) and positron emission tomography (PET) scanning sessions last long durations, motion blur during scanning constitutes a problem for clinical interpretation. To counteract this, motion-correction algorithms have been developed to reduce smearing between scan slices of MRI, but these algorithms are not commonplace for PET. This feasibility study determined if applying MRI motion-correction algorithms to simultaneously acquired PET data improved PET signal clarity in specific brain regions. Seven subjects received increasing levels of PET tracers while undergoing two separate simultaneous PET/MRI scans. We modified existing fMRI algorithms to apply them to the accompanying PET data. We hypothesized …

The Effect Of Endogenous Ligands Of The Aryl Hydrocarbon Receptor On Antibody Expression In A Human B-Cell Model, Valerie Benedict

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Small changes in antibody expression have broad impacts on human health and disease. An environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces profound immune suppression in animal models in an aryl hydrocarbon receptor (AhR)-mediated fashion. In a human Burkitt's lymphoma cell line (CL-01), TCDD inhibited IgG secretion and differentially impacted Ig heavy chain expression. In addition to TCDD, the AhR has several endogenous, dietary, and bacterial ligands such as 6-formylindolo[3,2-b]carbazole (FICZ) and indole, which are present within the human body at varied concentrations (0.30 mM- 6.64 mM). Both FICZ (100 nM) and indole (100 µM) significantly reduced IgG secretion. Overall antibody secretion is …

Characterization Of B3galt2 And Heg1 Expression In Dorsal Root Ganglia, Alexander H. Nguyen

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Proprioception provides unique sensory feedback about the body’s orientation in space and this sensation is essential for creating specific motor functions and coordinated movement. During neurogenesis, unique genetic markers are expressed and classified as early, transient/middle, and late markers depending on their timing of expression. This study focuses on the expression patterns of two late markers: Heg1 and B3galt2. We investigated how expression of these two markers respond to peripheral nerve injury (PNI). We cloned and generated riboprobes to detect expression of B3galt2 and Heg1 in DRGs using in situ hybridization after transection of the sciatic nerve. B3galt2 hybridization in …

The Role Of Igf-1 In Geriatric Skin, Amber Castellanos

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Keratinocytes are cells that largely occupy the epidermis layer of our skin and function to protect against DNA damage induced by ultraviolet radiation. Keratinocytes rely on the activation of the IGF-1 receptor in order to carry out an appropriate response to UV-B radiation. Keratinocytes themselves do not express the IGF-1 ligand; IGF-1 is produced by fibroblasts found in the dermis layer of the skin. With age, fibroblasts become senescent and this interferes with their ability to produce IGF-1 for the epidermal IGF-1R. This occurrence may aid in understanding why geriatric individuals are at greatest risk for developing nonmelanoma skin cancers, …

Impact Of Passive Range Of Motion Exercises And Stretching In Knee Osteoarthritis Pain During Walking, Dominique Marchelle Ottonello

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Knee osteoarthritis (KOA), is globally prevalent source of disability for the elderly. This degenerative malady progresses with age and has no cure. It manifests in gait changes and affects overall quality of life. Exercise therapy has been shown to improve knee joint range of motion, stiffness and pain due to KOA. This improvement is due in part to the direct relationship between muscle strength and joint stability. The purpose of this study is to examine how a passive range of motion (ROM) exercises and stretching regimens affect gait-alterations and associated pain from KOA experienced during walking. Nine KOA subjects were …

Assessment Of Pseudo-Continuous Arterial Spin Labeling (Pcasl) Inter-Session Reliability In The Quantification Of Cerebral Perfusion, Mohammad Ahmad Awad

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Arterial spin labeling (ASL) is a magnetic resonance imaging (MRI) technique used for measuring cerebral blood flow (CBF) in a completely non-ionizing and non invasive fashion. ASL is useful in perfusion studies on healthy adult & pediatric subjects, individuals who need multiple follow-ups, and patients with varying cerebrovascular diseases where changes in CBF can be used as an indicator of tissue viability. We used a variation of the ASL technique known as pseudo-continuous ASL (pCASL). This form of ASL is the clinical standard (Alsop et al., 2015). However, it is not well documented the that pCASL is reliable between sessions …

Social Buffering By Unfamiliar Adult Males In Periadolescent Guinea Pigs: The Effects On Hpa Axis Activity And Fos Induction In The Medial Prefrontal Cortex, Alexander Bertke

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In the guinea pig, the ability of the mother’s presence to buffer hypothalamic-pituitary- adrenal (HPA) axis activation in her young during exposure to stressful stimuli has been well documented. Under similar testing conditions, other conspecifics (littermates, other adult females) are less effective in doing so. The effect does seem to wane with age but is still present to a significant degree in offspring approaching adolescence. However, we recently observed that an unfamiliar adult male buffered HPA axis activation and increased Fos expression in the prefrontal cortex of preweaning infants exposed to a novel enclosure at both 60 and 120 minutes …

Effect Of Hybrid/Complex N-Glycosylation On Cardiac Voltage-Gated Ion Channel Expression, Austin R. Parrish

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Dilated cardiomyopathy (DCM) is one the most common forms of heart failure, with the majority of cases being idiopathic. Dr. Bennett’s laboratory previously showed that deletion of the Mgat1 gene in cardiomyocytes only (Mgat1KO) is sufficient to cause DCM leading to heart failure and early death. The Mgat1 gene product, GlcNAcT1, is responsible for initiating the formation of hybrid/complex N-glycosylation. These data suggest a link between abnormal glycosylation and heart disease; however, there is a mystery of how the specific changes in glycosylation contribute to heart disease etiology and progression. The proper function and gating of voltage-gated Na+ channels (Nav) …

The Effect Of Soleus Fatigue During Sidestep Cutting Maneuvers: Implications For The Acl, Michael William Ciesa

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The soleus muscle is a monoarticular plantarflexor composed slow-twitch fatigue-resistant muscle fibers. Through its attachment to the proximal tibia, contraction of the soleus muscle in a closed kinetic chain (when the foot is planted) produces a posterior pulling force on the posterior proximal tibia. The anterior cruciate ligament (ACL) is responsible for preventing anterior displacement of the tibia relative to the femur. Through the production of a posterior pulling force on the tibia, soleus muscle contraction in a closed kinetic chain could help reduce strain on the ACL. Fatigue is a neuromuscular phenomenon that can alter biomechanical strategies during athletics …

The Influence Of Static Stretching Of Knee Flexors On Knee Biomechanics, Joshua David Perrin

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There is a greater incidence of non-contact anterior cruciate ligament (ACL) injury in female athletes compared to males. The higher rate of ACL injury in female athletes is most likely multifactorial and is influenced by intrinsic and extrinsic risk factors. This study examines the effects of an extrinsic factor — static stretching of the hamstrings on knee biomechanics. Twelve female athletes performed drop vertical jump (DVJ) tasks before and after a hamstrings static stretching protocol. Knee kinematics and kinetics were recorded during the contact phase of the DVJ. The results of this study revealed stretching had no significant effect on …

Analysis Of Stretch Reflex Responses In Mice Lacking Munc18-1 In Proprioceptors, Amr Mohi

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The monosynaptic stretch reflex circuit is one of the simplest circuits of the central nervous system. We studied the connection between Ia proprioceptive afferents and motor neurons that comprise the circuit, by stimulating the dorsal root and recording from the ventral root of the fourth lumbar spinal nerve. In our study, we analyzed the status of neurotransmission in the stretch reflex circuit in postnatal PV-cre; munc18-1 lox/lox conditional mutant mice. Munc18-1 is responsible for synaptic vesicular release in neurons. In the PV-cre; Munc18-1 lox/lox mutants we use, Munc18-1 is only knocked out in proprioceptive afferents and A-beta somatosensory afferents, both …

Effects Of Abstraction And Assumptions On Modeling Motoneuron Pool Output, John Michael Allen

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Computational modeling has long been used in neuroscience as a supplement to more traditional experimental techniques, as it provides some advantages in terms of the level and detail of control available over the system being studied. At the same time, modeling has significant disadvantages by virtue of adding additional uncertainty to results and forcing the definition of potentially unclear physiological mechanisms. Nevertheless, modeling can provide useful insights when carefully defined and constrained. In this thesis, a model of the a-MN pool innervating the cat medial gastrocnemius was constructed. This model was then used to address two major questions, one regarding …

The Influence Of Age At Menarche And Hamstrings Fatigue On Knee Biomechanics, Stephanie Eileen Field

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Anterior cruciate ligament (ACL) injury is 4-8 times more likely to occur in females than in males and is associated with significant morbidity. The mechanism underlying the gender disparity in non-contact ACL injuries is likely multifactorial, and may be influenced by a variety of risk factors. This study examines the influence of age at menarche and neuromuscular fatigue of the hamstrings muscles on knee biomechanics. Twelve female athletes performed drop vertical jump (DVJ) tasks before and after a fatiguing protocol utilizing a glute-ham bench. Knee kinematics and kinetics were recorded during the contact phase of the DVJ. The results of …

Translocation And Phosphorylation Of Ampa Receptors Following Transcranial Direct Current Stimulation In Vivo, Justin Andrew Stafford

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Transcranial direct current stimulation (tDCS) is the current technique used clinically to attenuate the effects of various neurological related deficits and augment functions such as memory and learning. The cellular and molecular mechanisms behind tDCS remain largely unknown and this study provides some of the first insights into the mechanisms behind tDCS. Direct current stimulation has been used to increase levels of long term potentiation (LTP) ex vivo suggesting that this stimulation has an effect on the LTP mechanisms of action. Subcellular protein extraction and fractionation methods were used to isolate synaptoneurosomes from various brain regions to assess the effects …

The Timing Of Fluoxetine, Simvastatin And Ascorbic Acid Administration In A Post-Ischemic Stroke Environment Affects Infarct Volume And Hemorrhagic Transformation Frequency, Neal R. Verma

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Previous animal experiments have indicated that administration of fluoxetine and simvastatin at 20-26 hours post-stroke decreases the volume of ischemic infarcts. This experiment expanded on previous experiments by adding ascorbic acid to the post-stroke regimen, initiating simvastatin pre-stroke, and adding a third initiation time frame (48-54 hours). Male retired breeder Sprague-Dawley rats were on simvastatin for 7 days prior to stroke induction. Combined medications of 5 milligrams/kilogram of fluoxetine, 1 milligram/kilogram of simvastatin and 20 milligrams/kilogram of ascorbic acid were orally administered at 6-12 hours, 20-26 hours, or 48-54 hours, respectively, following stroke induction. Adult rats that were treated 20-26 …

Connectivity Of Monosynaptic Ia Afferents On Renshaw Cells In Neonatal Mice, Todd Joseph Rapetti

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Proprioception allows sensory information about muscle position and length to enter the CNS without the aid of visual cues. One type of fiber that carries this information is the Ia afferent, which innervates muscle spindles that respond to mechanical perturbation in muscle. Ia fibers are known to synapse with Ia interneurons (INs) and motor neurons (MNs), setting up important circuits which affect movement. Another type of IN is the Renshaw cell (RC), which is located in the ventral part of lamina VII of the spinal cord and is critical for the functionality of the recurrent inhibitory circuit. In addition to …

The Inhibitory Effects Of Opioids On Voltage-Gated Calcium Influx In Neonatal Rat Carotid Body Type I Cells, Ellen M. Ricker

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It is known that opioids inhibit the hypoxic ventilatory response, but little is known about the mechanisms that underpin this. This study's objectives were to examine which opioid receptors are located on the oxygen-sensing carotid body type I cells and determine whether selective agonists inhibit cellular excitability.

Immunocytochemistry revealed the presence of μ and κ opioid receptors on type I cells. The μ-selective agonist DAMGO (10μM) and the κ-selective agonist U50-488 (10μM) significantly (p<0.0025 and p<0.0095 respectively, unpaired student's t-test) inhibited high K+ induced rises in intracellular Ca2+ compared with controls. After a three-hour incubation with pertussis toxin, a Gi protein-coupled inhibitor, DAMGO and U50-488 (10μM) has no significant effect on the responses to K+.

These results indicate that opioids acting at μ and κ receptors inhibit voltage-gated Ca2+ influx in carotid body type I cells. This mechanism may explain, in …

Angiotensin-Ii Receptor Blocker And Its Effects On Depressive-Like Behavior During Maternal Separation, Evan D. Xanthos

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Maternal separation has been shown to promote the onset of adult depression. This early life stressor produces a biphasic response marked by an active "protest" phase followed by a passive "despair" phase in humans and other species. In infant guinea pigs, active phase behaviors include increased locomotion and distress vocalizations, whereas the passive phase is marked by depressive-like behaviors including a crouch stance, eye closure and piloerection. Separation elicits physiological responses including increased core body temperature and proinflammatory cytokine expression suggesting fever. Angiotensin-II receptor blockers (ARB's) inhibit inflammation both peripherally and centrally following peripheral administration. The goal of the present …

Is Polyvinylidene Diflouride (Pvdf) Film Biocompatible In The Murine Cochlea?, Robert Maxwell Jaggers

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Polyvinylidene fluoride (PVDF) film, a biomaterial that is an integral part of a Totally Implantable Sustainable Hearing Aide (TISHA) device, was examined to determine its biocompatibility within the murine cochlea. The biofilm was implanted in the ear using a round window cochleostomy in 7-9 week old male C57BL/6 mice. Three test groups containing seven mice each were implanted with PVDF film. Each mouse received a sham surgery on the non-implanted cochlea. Three test groups were examined at 48 hours, 3 weeks, and 3 months. At the end of this time the mouse was euthanized, the tissue containing the cochlea was …

Efficacy Of Mastery-Based And Autonomy-Supportive Neuroanatomy Curriculum In Graduate Level Human Neurobiology Course, Corin Wolfgang Magee

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Anatomy provides scientists with a common vocabulary for discussing the human body, and is, therefore, an important aspect of science education. Literature shows that traditional teaching methods may be enhanced by the employment of mastery-based learning in an autonomy-supportive environment. The present study sought to determine the effects of these teaching strategies on the learning of neuroanatomy in a graduate neurobiology course.

These results show students learned and reportedly enjoyed learning a large amount of neuroanatomy. Experimentally taught students who completed the curriculum did well on the 30-item neuroanatomy quiz (mean score 81%), which was administered at the end of …

Mechanisms Of Hyperglycemia-Induced Ros Production In Osmotically Swollen Glial Cells, Augusta K. Eduafo

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Cerebral edema is a potentially fatal complication of diabetes. There is evidence for increased Reactive Oxidative Species (ROS) production during cerebral edema in diabetics. This can lead to oxidative stress, thought to contribute to the onset and progression of diabetes and can cause cell injury and cell death. ROS, in moderate amounts, are involved in physiological processes within the body that produce favorable cellular responses. Unfortunately, high levels of ROS can lead to cellular damage of lipids, membranes, proteins and DNA. Hyperglycemia can cause an increase in ROS production due to activation of NADPH oxidases. The purpose of this study …

Effects Of Delayed Pharmacological Treatment And Limb Rehabilitation On Infarct Size And Functional Recovery After Stroke, Maria Helen Harley Balch

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Previous studies show a fluoxetine/simvastatin drug combination successfully reduced infarct size and increased functional recovery when administered 20-26 hours post stroke. This project tested the hypothesis that earlier drug delivery at 6-12 hours post stroke will improve functional recovery and decrease infarct size, and that limb rehabilitation will improve functional recovery.

Pre-stroke function was determined in rats, a stroke was induced, and daily treatment began 6-12 hours post stroke. Baseline functional deficit was established, and additional testing over 90 days monitored functional recovery. Limb rehabilitation was provided for designated animals, and brain analysis measured infarct size.

In animals with no …

Effect Of Rat Strain Stereotactic Coordinates On Infarct Volume, Saagar K. Sanghvi

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Ischemic stroke makes up 87% of all hospital-admitted stroke cases annually; the primary treatment for these cases is intravenous administration of tPA within a 3.5 hour window from stroke onset. A long-term delayed ischemic stroke treatment proposed by this study was a combination of the pharmaceuticals Fluoxetine (SSRI), Simvastatin (statin), and ascorbic acid (Vitamin C). 51 adult rat subjects (10-12 months of age; 44 Sprague Dawley, 7 Long Evans) were given a combination of the drugs for 31 days. Drugs were given through voluntary oral administration via sugar cookie-dough balls to reduce inhibition of neurogenesis through stress-related glucocorticoid production. Drug …

Characterization Of Stimulation-Induced Volume Changes In The Ca1 Region Of Rat Hippocampus Slices, Amanda Brooke Gutwein

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Intrinsic optical signals (IOS) were used to evaluate volume regulation mechanisms during Schaffer collateral stimulation-induced volume changes in hippocampal slices. The effects of stimulation frequency, synaptic function, ionotropic glutamate receptor (iGluR) activation, glutamate uptake, and volume regulatory anion channels (VRAC) were examined with IOS. Data were analyzed using ANOVA with Dunnett's post hoc test (p<0.05 indicated significance). IOS changes were stimulation frequency dependent between 1 Hz and 10 Hz with full recovery of IOS within 5 min. Synaptic blockage reduced the rate of swelling by 81% compared to the control and the IOS did not fully recover. Recovery rate was reduced with iGluR inhibition. Inhibition of glutamate uptake reduced the rate of swelling by 70% compared to vehicle controls. During stimulation, action potentials, iGluR activation, and glutamate uptake contribute to swelling. Regulatory volume mechanisms during stimulation were glutamate-mediated via iGluRs and VRAC independent.

C-Bouton Coverage Of Alpha-Motoneurons Following Peripheral Nerve Injury, Esra Salah Shermadou

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Peripheral nerve injuries (PNI) cause alternations in central synapses leading to loss of function. The C-bouton synapses onto a-motoneurons in the ventral horn, and has a role in regulating motor output. Following tibial nerve ligation, the somatic C-bouton coverage is depleted (Alvarez et al., 2011), however, it is unknown what happens following crush type injuries. PNI causes neuroglia activation and proliferation that contribute to synaptic alterations, a response that has not been well-characterized in the ventral horn, where motoneurons are located. Therefore, I hypothesize that glia activation following peripheral nerve injury correlates to the degree of depletion of synaptic coverage …

The Role Of Corticotropin-Releasing Factor In The Behavior And Proinflammatory Activity Of Separated Guinea Pig Pups, Vincent Rasahd Alexander

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Isolation of guinea pig pups in a novel environment first produces active behaviors such as vocalizing and movement; over time, these behaviors wane and pups show characteristic passive responses similar to those produced by increased proinflammatory activity. Further, isolation of pups on two consecutive days has recently been shown to enhance those passive responses on the second day. Endogenous proinflammatory activity is thought to mediate the enhancement (sensitization). An injection of corticotropin-releasing factor (CRF) has been shown to increase passive behavior, possibly by increasing proinflammatory activity. The present study further investigated the role of CRF on proinflammatory activity and behavior …

Maturation Of The Carotid Body Oxygen-Sensor During Rat Development, Julia Paulet

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Carotid bodies (CB) are paired, oxygen-sensing organs located in the bifurcation of the carotid artery that act as peripheral chemoreceptors in the detection of hypoxic, hypercapnic and acidotic levels in the arterial blood. CBs respond to these fluctuations in blood gases by initiating firing of the carotid sinus nerve. This ultimately results in the appropriate ventilatory change to restore blood gases to their physiological levels. Studies have shown that the hypoxic response of the carotid body in juvenile mammals is low, but as maturation occurs this response is strengthened and clearly exhibited in adults. One theory suggests mitochondria play a …

Effects Of Elevated Glucocorticoid Levels On Dentate Gyrus Development, Zachary Dale Vallandingham

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Exogenous glucocorticoids are commonly used in modern medications and animal studies examining the effects of glucocorticoids on the developing brain report inconsistent results. Recent reports have questioned the reliability of available drug delivery methods in mice (Herrmann et al., 2009). In our laboratory, variable behavioral results using trace eyeblink conditioning (EBC) suggest that we may be having similar problems delivering glucoroticoids to developing rat pups (Claflin et al., 2005, 2011). Subcutaneous pellets and osmotic minipumps resulted in impaired learning during trace eyeblink conditioning whereas subcutaneous injection of corticosterone (CORT) resulted in facilitation of learning on the same task. One of …