Browsing by Subject "Sensory"
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Item Anatomical and Optogenetic Investigations of Periglomerular Sensory Fibers in the Mouse Kidney(2022-06) Tyshynsky, RomanThough sensory-specific renal denervation has been shown to lower blood pressure in some animal models of hypertension, indicating their importance in the development and maintenance of hypertension, the anatomical distribution and function of sensory renal nerve fibers have not been fully elucidated. Both the anatomical and physiological study of sensory renal nerves have previously focused on sensory nerves innervating the renal pelvis due to their density within the pelvis wall. However, previous studies have described the presence of sensory fibers in the renal cortex but did not quantitatively or functionally investigate this cortical innervation. To begin to address the question of the importance of sensory fibers in the renal cortex, I first used immunohistochemical, and tissue clearing techniques to quantitatively describe the anatomical relationship between sensory fibers and glomeruli. I showed that a majority of mouse renal glomeruli, regardless of their depth within the renal cortex, present with a nearby TRPV1+ or CGRP+ sensory fiber. High-resolution imaging of cleared tissue and three-dimensional distance transformation techniques revealed that sensory fibers travel within a few microns of the Nephrin+ signal of glomerular podocytes and come in close contact with multiple glomeruli that share a common interlobular artery. These anatomical results suggest that periglomerular sensory fibers may function in a mechanosensitive manner to monitor glomerular pressures. To attempt to determine their physiological function, I designed an optogenetic device that was implemented in an anesthetized mouse preparation to measure the effects of optogenetic stimulation of TRPV1+ cortical sensory fibers on cortical blood flow, mean arterial pressure, and renal vascular resistance. Additional experiments validated the ability of this preparation to detect expected changes in these measurements with the subcapsular injection of vasoactive substances, the presence of channelrhodopsin in cortical sensory fibers, the functionality of channelrhodopsin-containing TRPV1+ sensory fibers via optogenetic activation of the baroreflex, and the ability of our chosen light source to penetrate the depth of the renal cortex. Nonetheless, the method used for optogenetic stimulation of TRPV1+ fibers in the mouse renal cortex did not elicit significant changes in cortical blood flow, arterial pressure, or renal vascular resistance from baseline values. These inconclusive results indicate that either the TRPV1+ fibers were never sufficiently stimulated by the delivered light, or that their acute activation does not result in measurable short-term changes in the measured values. Taken together, the discovery of sensory fibers near most glomeruli and currently inconclusive results of a novel attempt to stimulate TRPV1+ cortical sensory fibers in a spatial, temporal, and subtype-specific manner indicates that our understanding of the anatomical distribution and function of sensory renal nerves requires additional investigation. A more thorough understanding of sensory renal nerve anatomy and function will also likely improve treatments for renal nerve-based diseases like hypertension.Item Differential regulation of opioid receptors during inflammation(2009-07) Satterfield, Catherine SuzanneProperties of the opium poppy have been exploited for centuries for the alleviation of pain and to induce euphoria. Classically thought to produce its effects solely in the central nervous system, peripheral opioid analgesic systems are now widely accepted. The activation of these systems leads to a reduction in primary afferent fiber excitability leading to the inhibition of sensory transduction. Opioid receptors function is modulated by a variety of mechanisms. An example of this is enhanced peripheral opioid receptor function following inflammation. The present study examined peripheral opioid receptor regulation in early and late stages of CFA inflammation. Additionally, a new model of UVB of inflammation was characterized. Peripheral MOR receptors are differentially regulated in late and early CFA inflammation. Peripheral MOR is not responsible for attenuated responses of nociceptors to mechanical stimuli 18 hours after CFA inflammation. DAMGO reduced mechanical responsiveness of nociceptors at 72 hours after CFA inflammation in a concentration and antagonist reversible manner indicating that MOR efficacy is enhanced during later stages of CFA inflammation. UVB produced severe but localized inflammation that differed from inflammation produced by CFA. This inflammation sensitizes nociceptor units innervating irradiated skin and results in enhanced peripheral opioid receptor efficacy.Item Pain and sensory function in neuronal ceroid lipofuscinosis(2013-01) Burkitt, Chantel C.Aims: In individuals with Neuronal Ceroid Lipofuscinosis (NCL; Batten disease), a rare neurodegenerative disorder, to explore 1) the pain experience, 2) the relationship between pain and self-injurious behavior (SIB), 3) the degree of sensory reactivity, and 4) the degree of sensory reactivity in comparison to individuals without NCL. Method: Following informed consent, eight participants with NCL (M age= 14.8 years, range=8-22) were characterized in terms of pain experience (frequency, type, intensity, interference, expression, and coping) and severity of SIB. A brief sensory test (light touch, repeated Von Frey monofilament) was conducted with each participant with NCL as well as with a sibling comparison group without NCL (n=8, M age= 23.5 years, range = 8-37). During sensory testing, pain expression was measured using the Battens Observational Pain Scale (BOPS) and infrared thermography (IRT) was used to quantify changes in skin/eye temperature. Results: Individuals with NCL experienced pain frequently and from multiple sources that most negatively impacted enjoyment of life, mood, sleep, and social interactions. Individuals with NCL were significantly more likely to express their pain using vocal/social pain behaviors rather than body and limbs (p<.05) or physiological behaviors (p<.01). When in pain, individuals tended to seek social support more often. Individuals with NCL who had moderately severe SIB showed significantly more pain behaviors than individuals with mild or no SIB (p<.05). Individuals with NCL were reactive to the sensory testing as IRT temperatures significantly increased (p<.001). Across combined conditions (light touch, repeated Von Frey), individuals with NCL were significantly more reactive (BOPS total score) to sensory testing compared to individuals in the sibling comparison group (p< .05). Similarly, IRT difference scores between sensory conditions revealed a significant increase in temperature at all face/eye sites for individuals with NCL compared to siblings (p<.001). Interpretation: In this sample of individuals with NCL pain was intense and frequent with multiple sources that interfered with a range of daily activities. Individuals with moderately severe SIB may be more sensitive to pain or may experience more pain in general. BOPS scores were elevated prior to sensory testing suggesting that individuals with NCL are living with ongoing pain. The increased pain expression during the repeated application of the Von Frey filament, a partial test of central sensitization, further suggests that the pathophysiology of the ongoing pain individuals with NCL are living with is likely centrally not peripherally mediated.Item Sensory Features in Autism Spectrum Disorder: A Systematic Review of Measurement Quality and Empirical Investigation of Sensory Responsivity in Children at High and Low Familial Risk for Autism(2021-12) Gunderson, JaclynAutism spectrum disorder (ASD) is a complex neurodevelopmental disorder with heterogenous presentation and varying outcomes for children impacted by the condition. The etiology and bio-mechanisms of autism are not well understood. For decades research has focused on the social, communication, and cognitive symptoms associated with ASD. However, sensory symptoms were added to the diagnostic criteria for ASD in 2013 and continue to gain research attention. Historically, sensory symptoms were thought to emerge as secondary consequences of social-cognitive deficits. However, recent empirical work suggests that sensory symptoms manifest early in development and may contribute to the heterogeneity of ASD. For this dissertation, I systematically reviewed the literature to appraise the quality of proxy report sensory measurement tools used to assess sensory features in ASD. Furthermore, in a sample of children with a high and low familial likelihood for developing ASD, I characterized sensory responsivity in social and non-social contexts early in life and investigated the development of sensory responsivity throughout childhood with considerations for variables that may relate to developmental changes and their association with later adaptive behavior. Results from the current studies indicate that proxy report sensory questionnaires attempt to quantify sensory features in ASD via vastly different dimensions with little attention given to either construct or structural validity. Moreover, results show that sensory responsivity behaviors emerged across social and non-social contextual domains early in life and relate to restricted and repetitive behavior and adaptive behavior later in toddlerhood. Compared to children without ASD, children with ASD tend to demonstrate more early sensory responsivity behaviors that increase in a curvilinear relation to chronological age with specific trajectory differences across responsivity behavior patterns (hyperresponsivity, hyporesponsivity, sensory seeking). Additionally, heightened hyporesponsivity in the first year of life predicts lower adaptive behavior later in childhood. Specifically, results suggest that sensory features emerge prior to the consolidation of broad ASD symptoms and relate to adaptive outcomes. However, construct dimensions including the un-agreed upon multidimensionality of sensory features has important implications for future understanding and clinical practice.Item Shelf life analysis of cereal products processed with and without BHT(2020-08) Baumann, SamanthaThe use of butylated hydroxytoluene (BHT) has been used in packaging material of consumer packaged goods for decades. Incorporating antioxidants in ready-to-eat cereal products can inhibit oxidation and extend product shelf life. Interest in natural antioxidants has developed over the past few years due to potential risks to consumer health. Despite these risks, BHT remains on the generally recognized as safe (GRAS) list for now, and is a proven way to achieve the desired quality that consumers expect. The objective of this study was to understand the shelf life reliability of BHT in in four cereal products via application of BHT in two cereal components: the canola oil and the packaging film material. Additionally, this study explored the effects of BHT in cereals prepared using different formulae as well as different processing technology. Loose sensory testing was performed on four different cereal products with a focus on descriptors that are indicative of lipid oxidation such as cereal rancidity, off flavor/aroma, and flavor intensity. Analysis of variance and t-test statistical analyses were used to determine the significance of sensory data. BHT was found to affect different cereal products differently. Overall, the use of BHT in packaging material significantly improved the shelf life of breakfast cereal, while the use of BHT in canola oil showed little benefit to product shelf life. The results of this study will provide a baseline for companies looking to reduce or remove BHT from their cereal products.