891 |
Mechanisms Regulating Transient Receptor Potential Cation Channel A1 (TRPA1) and Their Roles in Nociception and Nociceptive SensitizationShang, Ye 26 June 2020 (has links)
Nociception is the sensory nervous system that detects harmful stimuli including excessive heat, cold, toxic chemicals, and noxious mechanical stimulations. Transient receptor potential (TRP) channels are a group of evolutionarily conserved ion channels consisting of 4 subunits, each with 6 transmembrane spans, and detect a variety of external and internal nociceptive stimuli. Due to their critical roles in nociception, it is essential to understand the mechanisms that regulate TRP channels and subsequent nociception. Here, I investigated two distinct types of regulation of Drosophila transient receptor potential cation channel A1 (TrpA1): regulation via the expression of different TrpA1 isoforms, and via its binding with associated proteins. I found that one of the TrpA1 isoforms, TrpA1(E), inhibits the thermal responses of other TrpA1 isoforms in vitro. I also identified potential TrpA1 binding partners through Co- immunoprecipitation (Co-IP) and mass spectrometry analysis. These binding partners need further validation and characterization through biochemical, cellular, and behavioral assays to illustrate their roles in nociception, and may serve as potential drug targets for chronic pain.
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892 |
Modulating ApoE with Tissue Specific siRNAs in Alzheimer’s DiseaseFerguson, Chantal M. 31 March 2021 (has links)
Among many putative genetic risk variations reported to date, the ApoE4 allele remains the most common genetic risk factor for late-onset AD, and is associated with both an increase in incidence and a decrease in age of clinical onset. The majority of ApoE is produced in the: 1) central nervous system (CNS) by astrocytes to transport lipids between cells and modulate the inflammatory response; and 2) liver, where it facilitates lipid uptake into peripheral tissues via low-density lipoprotein (LDL) receptors. Consistent with its dual roles, genetic knockout of ApoE increases the risk for atherosclerosis, but it also dramatically improves AD phenotypes in mouse models.
Antisense oligonucleotide (ASO) based modulation of CNS ApoE has only marginal effects on AD phenotypes, suggesting that post-embryonic silencing of ApoE is not a viable therapeutic strategy. However, the recent development of novel CNS siRNA chemical structures enables widespread distribution and potent target silencing throughout the brain. Using this technology, we demonstrate that liver and brain ApoE pools are spatially and functionally distinct, and that complete silencing of brain, not liver, ApoE results in robust reduction of amyloid plaque formation, without impacting systemic cholesterol. Furthermore, RNAseq analysis shows minimal off target effects of the siRNAs and identifies immune modulation and metabolic alterations as potential mechanisms behind ApoE’s role in plaque formation and clearance.
Moving forward, these results build upon the rationale to modulate ApoE expression and provide the technology necessary to further evaluate the impact ApoE silencing in AD and other neurodegenerative diseases
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893 |
Role of Modulating Glutamate Transporters on Hydrocodone and Alcohol Co-Abuse inAlcohol-Preferring RatsAlshehri, Fahad January 2018 (has links)
No description available.
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894 |
Effects of Voluntary Physical Rehabilitation on Neurogenesis In SVZ And Functional Recovery After Ischemic StrokeBalakrishnan, Anuranjani 17 December 2018 (has links)
No description available.
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895 |
Quantitative Assessments of Avian Endocasts as Tools for Inferring Neuroanatomical Traits and Potential Functional CapabilitiesEarly, Catherine Michele 05 June 2019 (has links)
No description available.
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896 |
Generational Effects of Paternal Cocaine Use in MiceYaw, Alexandra M. 10 April 2019 (has links)
No description available.
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897 |
Tuning surface properties to optimize cell behavior for tissue engineering applicationsMotta, Cecilia Margarida Mendes 29 August 2019 (has links)
No description available.
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898 |
Photopotentiation of Ganglion Cell Photoreceptors and Pupillary Light ResponsesYuhas, Phillip Thomas 17 October 2019 (has links)
No description available.
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899 |
Parameter Classification and Analysis of Neuronal Systems with Astrocytic Modulation of BehaviourLumpkin, Robert 23 October 2019 (has links)
No description available.
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900 |
CHANGES IN HEMOGLOBIN AND EPIGENETIC CONTROL IN MULTIPLE SCLEROSISAlkhayer, kholoud 05 August 2019 (has links)
No description available.
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