Scholarship & Research
Permanent URI for this communityhttps://scholarworks.montana.edu/handle/1/1
Browse
10 results
Search Results
Item The impact of trait anxiety and psychosocial stress on sympathetic neural control in humans(Montana State University - Bozeman, College of Letters & Science, 2023) Bigalke, Jeremy Andrew; Chairperson, Graduate Committee: Cara A. Palmer; This is a manuscript style paper that includes co-authored chapters.Anxiety is highly prevalent, and while it is often adaptive, excessive stress and anxiety may predispose individuals to a heightened risk of cardiovascular disease. While excessive activity of the sympathetic nervous system (SNS) may underlie this association, direct measures of muscle sympathetic nerve activity (MSNA) indicate little, if any, alterations in resting sympathetic outflow in individuals with anxiety disorders. Assessment of the relationship between trait anxiety, MSNA, and blood pressure using a large cohort of healthy adults has not yet been conducted. Further, utilization of stress tasks within microneurographic settings that minimize the potential influence of breathing alterations, muscle movement, and other variables on the typically observed inter-individual variability in MSNA responsiveness to mental stress are needed to adequately assess the sole contribution of psychological stress on sympathetic neural activity. In Study 1, the association between trait anxiety, MSNA, and resting blood pressure was assessed in a population of 88 healthy adults, representing the largest study to date pairing trait anxiety with directly recorded sympathetic outflow to the periphery. Our findings indicate an independent relationship between trait anxiety, MSNA, and blood pressure when controlling for both age and sex. In Study 2, we utilized the trier social stress test (TSST) to assess the impact of anticipatory stress on MSNA and blood pressure in 28 healthy adults. Our findings showed that anticipatory stress is associated with increased blood pressure and reduced MSNA. Additionally, this appears to be baroreflex mediated as the magnitude of changes in blood pressure were directly proportional to reductions in MSNA, a relationship that was weakened or nonexistent during the active speech portion of the task. Lastly, anticipatory MSNA responsiveness accurately predicted reactivity to subsequent stress tasks. Together, these studies highlight a key relationship between both chronic, and acute psychological stress and anxiety on sympathoneural function in healthy adults.Item Determining function of the IKAP protein in the peripheral nervous system for targeted therapeutic intervention in familial dysautonomia(Montana State University - Bozeman, College of Letters & Science, 2017) Ohlen, Sarah Beth; Chairperson, Graduate Committee: Frances Lefcort; Magdalena L. Russell, Michael J. Brownstein and Frances Lefcort were co-authors of the article, 'BGP-15 prevents the death of neurons in a mouse model of familial dysautonomia' in the journal 'Proceedings of the National Academy of Sciences' which is contained within this thesis.Familial Dysautonomia (FD) is a recessive genetic disorder that leads to devastation of the peripheral nervous system and is the result of incomplete neurodevelopment and progressive neurodegeneration. The disorder is also marked by a continual loss of retinal ganglion cells that leads to blindness. Even with early identification and treatment, the disorder is ultimately fatal. FD is caused by mutation in the IKBKAP gene that leads to cell-type specific loss of the IKAP protein, also known as ELP1. IKAP functions as a part of the six-unit Elongator complex. The role of Elongator is unresolved, although data has accumulated that support Elongator function in tRNA modification and efficient translation of proteins and that its absence leads to cell stress and neurological impairment. We have a mouse model of FD in which mouse Ikbkap is deleted from the peripheral nervous system, and it recapitulates the death of autonomic and TrkA+ sensory neurons observed in FD patients. As we can culture TrkA+ neurons in vitro, while also studying this neuronal population in vivo, we have a system to investigate our goals of (1) determining cellular processes that go awry in absence of Ikap and (2) targeting these cell types and events to prevent their progressive death. We have determined that mitochondrial and cytoskeletal function are disrupted in Ikbkap -/-, TrkA+ neurons and show activation of stress signaling. Interestingly, disrupted mitochondrial function is an emerging hallmark common to most neurodegenerative diseases. We have identified that the compound, BGP-15, is able to restore aspects of mitochondrial function and stress signaling in vitro and can restore neuronal survival of TrkA+ neurons lacking Ikap in vitro and in vivo. BGP-15 also improves actin cytoskeletal function and target innervation. Additionally, we have determined that introduction of the C-terminal half of human IKAP is sufficient to increase neuronal survival in vitro. This smaller protein fragment is compatible with viral delivery to retinal ganglion cells and could be utilized for gene therapy, potentially preventing this neuronal death that lead to blindness. Our goals now are to further explore stress pathways common to many neurodegenerative disorders and optimize rescue strategies in vivo.Item Unilateral hypothalamic lesion results in compensatory sprouting of contralateral magnocellular neurosecretory axons in the rat neural lobe(Montana State University - Bozeman, College of Letters & Science, 1989) Watt, John AndrewItem Metabolic investigations of the hypothalamo-neurohypophysical system during axonal sprouting : efects of hyponatremia(Montana State University - Bozeman, College of Letters & Science, 1996) Moffett, Christopher WadeItem Dynamic expression of trk receptors during sensory neuron differentiation(Montana State University - Bozeman, College of Letters & Science, 1996) Rifkin, Jason ThomasItem Regrowth of rabbit optic nerve fibers after transection and peripheral nerve graft : an electron microscopic study(Montana State University - Bozeman, College of Letters & Science, 1983) Myron, Marie Elise LegareItem Educating registered nurses to perform monofilament exams on type 2 diabetics to detect peripheral neuropathy(Montana State University - Bozeman, College of Nursing, 2013) Stewart, Maria Lynn; Chairperson, Graduate Committee: Karen ZulkowskiDiabetic Peripheral Neuropathy (PN), a serious complication of diabetes, affects nearly 50% of diabetics. Complications of PN are pain, foot wounds, infection, and amputation of the lower extremity. These complications cost the healthcare system billions of dollars annually. Assessing for loss of sensation in the feet is an American Diabetes Association (ADA) standard of care. This exam is vital in preventing further complications and is done with a simple tool called the monofilament wire. Currently registered nurses are not educated in school or on the job on how to use this simple tool; therefore it is unknown how effective registered nurses could be at detecting PN. This study aimed to determine if registered nurses could be educated on the use of a monofilament tool and perform these exams accurately and obtain reliable results. Five registered nurses in an outpatient diabetes clinic were educated on how to perform a monofilament exam using recommendations by the ADA. The nurses performed practice exams on each other while being observed by the author. After successfully completing the education process they performed the exam on patients. The nurses performed 15 monofilament exams. A negative result indicates sensation in the feet is in tact. A positive indicates loss of sensation. The patient's primary care provider verified all 15 results obtained. The nurses' results were congruent 100% of the time when compared to the provider's. Of the 15 exams, 53% were positive and 47% were negative The results of this study indicate that nurses can be educated on how to perform the monofilament exam accurately, based on the verification of results by the primary care provider. Although a small sample size, the results show that the nurses picked up 53% of cases of loss of sensation, which will increase patient awareness and provide opportunity for education on foot health and how to prevent foot wounds and infections. Allowing the nurse to participate in this simple exam, as part of their assessment on diabetic patients, will increase the number of cases of PN detected, decrease costs to the healthcare system, and increase patient quality of life.Item Analysis of the expression and function of chicken protocadherin 1 in neural crest cell migration and peripheral nervous system formation(Montana State University - Bozeman, College of Letters & Science, 2007) Bononi, Judy; Chairperson, Graduate Committee: Roger Bradley.The necessary steps of development from a single cell to a multi-celled functional organism are complex. Many molecules have been identified and their roles characterized in this process. One interesting population of cells includes the highly migratory neural crest cells (NCCs) unique to the vertebrate embryo and existing transiently during early embryonic development. The NCCs migrate along specific pathways at specific timepoints, stop at target locations, differentiate and give rise to a variety of cell types and tissues. Trunk NCCs must choose between two different migratory pathways: the ventral route, giving rise to neurons and glia of the dorsal root ganglia (DRG), sympathetic ganglia (SG), Schwann cells of the ventral root (VR); or the dorsolateral pathway, giving rise to melanocytes. Although many aspects of neural crest migration have been elucidated, cessation of migration and subsequent differentiation at target structures is not clearly defined. One family of molecules involved in various steps of NCC migration is the cell-cell adhesion molecules, the cadherins. To investigate the involvement of cadherins in NCC migration and differentiation during development using the avian model system, a combination of experiments and techniques including a library screen, in situ hybridization, in ovo electroporation, immunohistochemical and immunofluorescence staining as well as live time-lapse confocal imaging were performed. Results from these experiments produced the discovery and isolation of a novel molecule in the family of cadherin adhesion molecules, chicken protocadherin-1 (cPcdh1). Expression analysis showed cPcdh1 expressed in migrating NCCs, the DRG, SG and Schwann cells along the VR. A distinct expression pattern showed cPcdh1 along the periphery of the DRG, where crest cells are in an undifferentiated and mitotically active state. Further testing with deletion constructs and siRNA demonstrated when cPcdh1 function is inhibited, a greater percentage of cells migrate to the SG and VR at the expense of the DRG. Time-lapse confocal imaging showed cPcdh1 cells having an elongated cell shape with contact primarily being formed with neighboring cells along the periphery and longer cell-cell contact than observed in the control. Collectively, the results provide evidence for cPcdh1 involvement in NCC migration arrest and DRG formation.Item Olfactory behavior as an indicator of prion infection(Montana State University - Bozeman, College of Letters & Science, 2011) Williams, Nikolas Scott; Chairperson, Graduate Committee: A. Michael BabcockThe current project sought to identify changes in olfactory-related behavior in hamsters infected with the HY transmissible mink encephalopathy (HY TME) strain of the pathological form of the prion protein. Experiment 1 was conducted to validate an olfactory preference paradigm for use with Syrian golden hamsters. An experimental group was induced with anosmia by treating them with methimazole. In an olfactory preference test in which the time subjects spent investigating attractive, aversive, and neutral olfactory stimuli were assessed, control animals spent a significantly longer amount of time investigating the attractive versus aversive scents. The methimazole-treated group did not demonstrate this pattern. Experiment 2 investigated changes in olfactory behavior as a result of prion infection. A group of hamsters was infected with HY TME and subjected to olfactory preference testing at four time points: 20, 40, 60, and 80 days post inoculation. In addition, parallel subjects were sacrificed and submitted to immunohistochemical analysis in order to examine the proliferation of HY TME throughout olfactory-related brain structures with the intention of relating behavioral changes to the progression of prion infection. Results indicated that HY TME subjects lost their ability to perceive the attractive scent early in the disease. However, avoidance of the aversive scent was retained until much later. The immunohistochemistry revealed an initial appearance of the pathologic prion at 20 days post inoculation in the glomeruli of the olfactory bulb. Widespread infection throughout all olfactory structures was observed at 40 days post inoculation and beyond. These results suggested a differential sensory loss to the olfactory stimuli that may have been due to initial infection in the glomeruli and later infection in other olfactory structures. These findings support the utility of discrimination paradigms for the diagnosis of prion diseases.Item Characterization of the neural codebook in an invertebrate sensory system(Montana State University - Bozeman, College of Letters & Science, 2007) Aldworth, Zane Nathan; Chairperson, Graduate Committee: John P. Miller; Tomas Gedeon (co-chair)An outstanding problem in neuroscience is to describe the relationship between various stimulus sources in the environment and how they are represented by patterns of activity in nervous systems, a problem generically referred to as 'neural coding'. Most previous methods developed to address this problem have assumed a linear relationship between environmental stimuli and neural responses, and generally relied on measures of the mean state of the environment preceding neural activity to characterize the stimulus-response transformation. The goal of this thesis is to develop new methods of characterization that extend earlier work, and to demonstrate the utility of these new methods through application to an invertebrate sensory system. All applications of the methods developed in this thesis were carried out in the cercal system of crickets. The cercal system mediates the detection and analysis of low velocity air currents, and is implemented around an internal representation of air current direction that demonstrates the essential features of a continuous neural map. The stimulus feature selectivity, timing precision and coding characteristics of two bilateral pairs of primary sensory interneurons of the cercal system were characterized using three novel techniques. First, estimates of the cells' feature selectivity that take the natural variance in stimulus-response latency (i.e., spike 'jitter') into account were derived. Second, the cells' stimulusresponse relationship was probed for specific non-linear aspects that could constitute 'temporal' encoding. Third, an iterative stimulation paradigm was used to test and refine the predictions of the cercal system's stimulus selectivity. Compared to earlier characterization of this system, these new analytical procedures yield significantly different estimates of the stimulus feature selectivity of these cells. A 'code book' for the stimulus-response characteristics of these cells is presented, with emphasis on demonstrating instances where a cell represents different stimuli with distinct spike 'code-word' patterns.