Life Sciences Commons^™

Characterization Of Vesicular Monoamine Transporter 2 And Its Role In Parkinson's Disease Pathogenesis Using Drosophila, Antonio Joel Tito Jr., Sheng Zhang

Dissertations & Theses (Open Access)

Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by the selective loss of the dopaminergic neurons in the Substantia nigra pars compacta region of the brain. PD is also the most common neurodegenerative disorder and the second most common movement disorder. PD patients exhibit the cardinal symptoms, including tremor of the extremities, rigidity, slowness of movement, and postural instability, after 70-80% of DA neurons degenerate. It is, therefore, imperative to elucidate the underlying mechanisms involved in the selective degeneration of DA neurons. Although increasing numbers of PD genes have been identified, why these largely widely expressed genes induce …

The Cellular Context Of Estradiol Regulation In The Zebra Finch Auditory Forebrain, Maaya Ikeda

Doctoral Dissertations

Estradiol, traditionally known as a hormone that communicates with distant cells in the body, is also synthesized locally in the brain to act as a neuromodulator. Neuromodulators differ from neurotransmitters in that they simultaneously affect a population of neurons and their actions are not limited to the synapse. One of the many effects of estradiol signaling is rapid modulation of auditory processing in response to external stimuli. The enzyme required for estradiol synthesis, aromatase, is highly expressed in the regions that are involved in higher-order processing of sounds in humans and songbirds. Since zebra finches, a type of songbird, are …

Non-Human Primates In Neuroscience Research: The Case Against Its Scientific Necessity, Jarrod Bailey, Katy Taylor

Jarrod Bailey, PhD

Public opposition to non-human primate (NHP) experiments is significant, yet those who defend them cite minimal harm to NHPs and substantial human benefit. Here we review these claims of benefit, specifically in neuroscience, and show that: a) there is a default assumption of their human relevance and benefit, rather than robust evidence; b) their human relevance and essential contribution and necessity are wholly overstated; c) the contribution and capacity of non-animal investigative methods are greatly understated; and d) confounding issues, such as species differences and the effects of stress and anaesthesia, are usually overlooked. This is the case in NHP …

Social Knowledge, Keith Jensen, Joan B. Silk, Kristin Andrews, Redouan Bshary, Dorothy L. Cheney, Nathan Emery, Charlotte K. Hemelrijk, Kay Holekamp, Derek C. Penn, Josef Perner, Christoph Teufel

Kristin Andrews, PhD

The social milieus of animals can be complex, ranging from almost completely asocial to monogamous pairs (no mean feat) to entire societies. To adapt to a constantly shifting environment of individuals striving toward their own goals, animals appear to have evolved specialized cognitive abilities. As appealing and intuitive as the idea of social cognition is, just defi ning it is diffi cult. We attempted to delineate social cognition, speculate on its adaptive value, and come to an understanding of what we mean when we talk about complexity. Transitive inference was often brought up as an example of a cognitive ability …

Consciousness: Where We Are At, Imants Barušs

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

It is useful every couple of years to take a bird’s eye view of consciousness studies and reflect on what we see. When I look, I still see two streams, one of which is the social and political framework for the study of consciousness, and the other of which is the substance of what we know about consciousness. The former is still largely defined by the extent to which the scientific study of consciousness has been freed from a materialist agenda. The latter includes recent research into the clarity of cognitive functioning in the absence of sufficient neurological support for …

Effects Of Glyceollin On Mrna Expression In The Female Mouse Brain., Sanaya Firdaus Bamji

Electronic Theses and Dissertations

Glyceollins (Glys), produced by soy plants in response to stress, have anti-estrogenic activity in breast and ovarian cancer cell lines in vitro and in vivo. In addition to known anti-estrogenic effects, Glys exhibit mechanisms of action not involving estrogen receptor (ER) signaling. To date, effects of Glys on brain physiology and function are unknown. The purpose of the experiments summarized in this dissertation was to gain an understanding of the effects of Gly on brain-related functions in the female mouse brain through the observation of changes in gene expression. For our initial studies, we treated ovariectomized Swiss Webster (CFW) …

Spider Brain Morphology & Behavior, Skye M. Long

Doctoral Dissertations

Spiders are ideal model animals for experimental and comparative studies of behavior, learning and perception. They display many complex behaviors, such as the multimodal mating dances of lycosid spiders, the stealthy hunting strategies of the jumping spider Portia sp., to the labile sociality of theridiids. Spiders also demonstrate a wide range of cognitive capabilities. Spiders perceive their environment using multiple sensory modalities including: chemosensory organs; lyriform and slit-sense organs and specialized hairs that detect vibration and air movement; and up to eight eyes that vary in function, some able to detect polarization and a broad spectrum of light, including …

Mutation Linked To Autosomal Dominant Nocturnal Frontal Lobe Epilepsy Reduces Low-Sensitivity Α4Β2, And Increases Α5Α4Β2, Nicotinic Receptor Surface Expression, Weston A. Nichols, Brandon J. Henderson, Christopher B. Marotta, Caroline Y. Yu, Chris Richards, Dennis A. Dougherty, Henry A. Lester, Bruce N. Cohen

Chemistry Faculty Publications

A number of mutations in α4β2-containing (α4β2*) nicotinic acetylcholine (ACh) receptors (nAChRs) are linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), including one in the β2 subunit called β2V287L. Two α4β2* subtypes with different subunit stoichiometries and ACh sensitivities co-exist in the brain, a high-sensitivity subtype with (α4)₂(β2)₃ subunit stoichiometry and a low-sensitivity subtype with (α4)₃(β2)₂ stoichiometry. The α5 nicotinic subunit also co-assembles with α4β2 to form a high-sensitivity α5α4β2 nAChR. Previous studies suggest that the β2V287L mutation suppresses low-sensitivity α4β2* nAChR expression in a knock-in mouse model and also that α5 co-expression …

Generation Of Organ-Conditioned Media And Applications For Studying Organ-Specific Influences On Breast Cancer Metastatic Behavior, Matthew M. Piaseczny, Graciella M. Pio, Jenny E. Chu, Ying Xia, Kim Nguyen, David Goodale, Alison Allan

Anatomy and Cell Biology Publications

Breast cancer preferentially metastasizes to the lymph node, bone, lung, brain and liver in breast cancer patients. Previous research efforts have focused on identifying factors inherent to breast cancer cells that are responsible for this observed metastatic pattern (termed organ tropism), however much less is known about factors present within specific organs that contribute to this process. This is in part because of a lack of in vitro model systems that accurately recapitulate the organ microenvironment. To address this, an ex vivo model system has been established that allows for the study of soluble factors present within different organ microenvironments. …

Modulating Neuronal Activity: Copper, Isoproterenol, And Beta-Blockers On The Brain, Veronica Go

Chancellor’s Honors Program Projects

No abstract provided.

Characterization Of A Silac Method For Proteomic Analysis Of Primary Rat Microglia, Ping Zhang, Ashley E. Culver-Cochran, Stanley M. Stevens Jr., Bin Liu

Molecular Biosciences Faculty Publications

Microglia play important and dynamic roles in mediating a variety of physiological and pathological processes during the development, normal function and degeneration of the central nervous system. Application of SILAC-based proteomic analysis would greatly facilitate the identification of cellular pathways regulating the multifaceted phenotypes of microglia. We and others have successfully SILAC-labeled immortalized murine microglial cell lines in previous studies. In this study, we report the development and evaluation of a SILAC-labeled primary rat microglia model. Although the isotope labeling scheme for primary microglia is drastically different from that of immortalized cell lines, our de novo and uninterrupted primary culture …

Network-Driven Plasma Proteomics Expose Molecular Changes In The Alzheimer's Brain, Philipp A. Jaeger, Kurt M. Lucin, Markus Britschgi, Badri Vardarajan, Ruo-Pan Huang, Elizabeth D. Kirby, Rachelle Abbey, Bradley F. Boeve, Adam L. Boxer, Lindsay A. Farrer, Nicole Finch, Neill R. Graff-Radford, Elizabeth Head, Matan Hofree, Ruochun Huang, Hudson Johns, Anna Karydas, David S. Knopman, Andrey Loboda, Eliezer Masliah, Ramya Narasimhan, Ronald C. Petersen, Alexei Podtelezhnikov, Suraj Pradhan, Rosa Rademakers, Chung-Huan Sun, Steven G. Younkin, Bruce L. Miller, Trey Ideker, Tony Wyss-Coray

Pharmacology and Nutritional Sciences Faculty Publications

Background: Biological pathways that significantly contribute to sporadic Alzheimer’s disease are largely unknown and cannot be observed directly. Cognitive symptoms appear only decades after the molecular disease onset, further complicating analyses. As a consequence, molecular research is often restricted to late-stage post-mortem studies of brain tissue. However, the disease process is expected to trigger numerous cellular signaling pathways and modulate the local and systemic environment, and resulting changes in secreted signaling molecules carry information about otherwise inaccessible pathological processes.

Results: To access this information we probed relative levels of close to 600 secreted signaling proteins from patients’ blood samples using …

“My Logic Is Undeniable”: Replicating The Brain For Ideal Artificial Intelligence, Samuel C. Adams

Senior Honors Theses

Alan Turing asked if machines can think, but intelligence is more than logic and reason. I ask if a machine can feel pain or joy, have visions and dreams, or paint a masterpiece. The human brain sets the bar high, and despite our progress, artificial intelligence has a long way to go. Studying neurology from a software engineer’s perspective reveals numerous uncanny similarities between the functionality of the brain and that of a computer. If the brain is a biological computer, then it is the embodiment of artificial intelligence beyond anything we have yet achieved, and its architecture is advanced …

Premises Of A Natural Science Of Consciousness, Ervin Laszlo

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

According to the mainstream of modern science, there cannot be a natural science of consciousness because consciousness does not actually exist in nature. It is a product or by-product of the workings of the brain. There is a natural science of brain and the nervous system, for these are bona fide elements of the world, but there cannot be a natural science of a phenomenon of which the very existence is in question. In the prevalent view con2sciousness is something that happens when neurons fire in the brain. This is said to be confirmed by experience. There is no consciousness …

Reembodying, Human Consciousness In The Earth, John Briggs

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

For the last 20,000 years or so the dominant mode of human consciousness has been one that divides reality into subjects and objects, and focuses on human desires and needs. This anthropocentric mode of consciousness has invented religions, built civilizations, amassed knowledge, and developed technology and science. It has also disembodied us from the Earth and led to the Anthropocene Era. Still with us is another mode of human consciousness that arguably once existed in a balance with the anthropocentric mode during our long hunter-gatherer, Paleolithic sojourn. This holistic, integrative mode of consciousness experiences the Earth as a mother, and …

Non-Human Primates In Neuroscience Research: The Case Against Its Scientific Necessity, Jarrod Bailey, Katy Taylor

Experimentation Collection

Public opposition to non-human primate (NHP) experiments is significant, yet those who defend them cite minimal harm to NHPs and substantial human benefit. Here we review these claims of benefit, specifically in neuroscience, and show that: a) there is a default assumption of their human relevance and benefit, rather than robust evidence; b) their human relevance and essential contribution and necessity are wholly overstated; c) the contribution and capacity of non-animal investigative methods are greatly understated; and d) confounding issues, such as species differences and the effects of stress and anaesthesia, are usually overlooked. This is the case in NHP …

Fish Pain's Burden Of Proof, Carl Safina

Animal Sentience

A hypothesis like Key’s, that fish cannot feel pain, should really be stated as a null hypothesis — an assumption that there is no difference in the things being compared. Then evidence — including anecdotal evidence — for and against rejecting the null hypothesis can be examined and weighed. Key (2016a) has proven only that fish lack mammalian brains.

Mw151 Inhibited Il-1Β Levels After Traumatic Brain Injury With No Effect On Microglia Physiological Responses, Adam D. Bachstetter, Zhengqiu Zhou, Rachel K. Rowe, Bin Xing, Danielle S. Goulding, Alyssa N. Conley, Pradoldej Sompol, Shelby Meier, Jose F. Abisambra, Jonathan Lifshitz, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

A prevailing neuroinflammation hypothesis is that increased production of proinflammatory cytokines contributes to progressive neuropathology, secondary to the primary damage caused by a traumatic brain injury (TBI). In support of the hypothesis, post-injury interventions that inhibit the proinflammatory cytokine surge can attenuate the progressive pathology. However, other post-injury neuroinflammatory responses are key to endogenous recovery responses. Therefore, it is critical that pharmacological attenuation of detrimental or dysregulated neuroinflammatory processes avoid pan-suppression of inflammation. MW151 is a CNS-penetrant, small molecule experimental therapeutic that restores injury- or disease-induced overproduction of proinflammatory cytokines towards homeostasis without immunosuppression. Post-injury administration of MW151 in a …

Modulatory Action By The Serotonergic System: Behavior And Neurophysiology In Drosophila Melanogaster, Zana R Majeed, Esraa Abdeljaber, Robin Soveland, Kristin Cornwell, Aubrey Bankemper, Felicitas Koch, Robin L. Cooper

Biology Faculty Publications

Serotonin modulates various physiological processes and behaviors. This study investigates the role of 5-HT in locomotion and feeding behaviors as well as in modulation of sensory-motor circuits. The 5-HT biosynthesis was dysregulated by feeding Drosophila larvae 5-HT, a 5-HT precursor, or an inhibitor of tryptophan hydroxylase during early stages of development. The effects of feeding fluoxetine, a selective serotonin reuptake inhibitor, during early second instars were also examined. 5-HT receptor subtypes were manipulated using RNA interference mediated knockdown and 5-HT receptor insertional mutations. Moreover, synaptic transmission at 5-HT neurons was blocked or enhanced in both larvae and adult flies. The …

Brain Processes For “Good” And “Bad” Feelings: How Far Back In Evolution?, Jaak Panksepp

Animal Sentience

The question of whether fish can experience pain or any other feelings can only be resolved by neurobiologically targeted experiments. This commentary summarizes why this is essential for resolving scientific debates about consciousness in other animals, and offers specific experiments that need to be done: (i) those that evaluate the rewarding and punishing effects of specific brain regions and systems (for instance, with deep-brain stimulation); (ii) those that evaluate the capacity of animals to regulate their affective states; and (iii) those that have direct implications for human affective feelings, with specific predictions — for instance, the development of new treatments …

Fish Brains And Behaviour Indicate Capacity For Feeling Pain, Donald M. Broom

Animal Sentience

Abstract: Studies of behaviour are of major importance in understanding human pain and pain in other animals such as fish. Almost all of the characteristics of the mammalian pain system are also described for fish. Emotions, feelings and learning from these are controlled in the fish brain in areas anatomically different but functionally very similar to those in mammals. The evidence of pain and fear system function in fish is so similar to that in humans and other mammals that it is logical to conclude that fish feel fear and pain. Fish are sentient beings.

Pain In Fish: Weighing The Evidence, James D. Rose

Animal Sentience

The target article by Key (2016) examines whether fish have brain structures capable of mediating pain perception and consciousness, functions known to depend on the neocortex in humans. He concludes, as others have concluded (Rose 2002, 2007; Rose et al. 2014), that such functions are impossible for fish brains. This conclusion has been met with hypothetical assertions by others to the effect that functions of pain and consciousness may well be possible through unknown alternate neural processes. Key's argument would be bolstered by consideration of other neurological as well as behavioral evidence, which shows that sharks and ray are fishes …

Fish Pain: A Painful Topic, Carl Safina

Animal Sentience

If fish cannot feel pain, why do stingrays have purely defensive tail spines that deliver venom? Stingrays’ ancestral predators are fish. And why do many fishes possess defensive fin spines, some also with venom that produces pain in humans? These things did not evolve just in case sentient humans would evolve millions of years later and then invent scuba. If fish react purely unconsciously to “noxious” stimuli, why aren’t sharp jabbing spines enough? Why also stinging venom?

Predicting The Knowledge–Recklessness Distinction In The Human Brain, Iris Vilares, Michael J. Wesley, Woo-Young Woo-Young Ahn, Richard J. Bonnie, Morris B. Hoffman, Owen D. Jones, Stephen J. Morse, Gideon Yaffe, Terry Lohrenz, Read Montague

All Faculty Scholarship

Criminal convictions require proof that a prohibited act was performed in a statutorily specified mental state. Different legal consequences, including greater punishments, are mandated for those who act in a state of knowledge, compared with a state of recklessness. Existing research, however, suggests people have trouble classifying defendants as knowing, rather than reckless, even when instructed on the relevant legal criteria.

We used a machine-learning technique on brain imaging data to predict, with high accuracy, which mental state our participants were in. This predictive ability depended on both the magnitude of the risks and the amount of information about those …

Gβγ Dependent Modulation Of Cytoskeleton And Neurite Outgrowth Involves The Pi3k/Akt/Gsk-3Β Pathway, Jose L. Varela

Open Access Theses & Dissertations

Assembly and disassembly of microtubules is critical for axon and dendrite formation and neurite outgrowth. Previous studies have shown that βγ subunits of heterotrimeric G proteins promote microtubule (MT) assembly in vitro and in cultured PC12 cells. Recently, it was found that the interaction of Gβγ with MTs is important for nerve growth factor (NGF)-induced neuronal differentiation of PC12 cells and that the blocking of the interaction between Gβγ and tubulin/MT disrupted MTs, inhibited neurite outgrowth and induced axonal damage indicating the involvement of Gβγ in these processes. A different pathway involving the receptor tyrosine kinase (TrkA) and its downstream …

An Investigation Of The Uptake, Distribution, And Accumulation Of Lead And Other Trace Elements In Caprine Brain Tissues Using Analytical Atomic Spectrometry, Amy Joanna Steuerwald

Legacy Theses & Dissertations (2009 - 2024)

Exposure to toxic elements and dysregulation of essential elements have been implicated in neurodegenerative disorders. Despite the importance of trace elements in neurological function, little is known regarding their uptake and distribution within brain tissues. Even less is known regarding the impact of toxic metal exposure (i.e., Pb) on endogenous metals within the brain.

The Use Of Doublecortin To Quantify The Effects Of Pharmacological Treatment On Neurogenesis And Functional Recovery After Stroke, Amber Lee Hensley

Browse all Theses and Dissertations

Ischemic strokes account for 87% of all strokes and can have debilitating effects on language, sensory, and motor skills. Currently, tPA is the only medication approved by the FDA for the treatment of ischemic stroke, but the window of time to administer the drug is very small. In this thesis, we investigate the use of a simvastatin and fluoxetine drug combination (FS) as a possible treatment for ischemic stroke victims. To analyze the effects of FS on neurogenesis and functional recovery, we utilize the Montoya Staircase and quantify the amount of neurogenesis using doublecortin. Although the results of this study …

The Effects Of Cold And Freezing Temperatures On The Blood Brain Barrier And Aquaporin 1, 4, And 9 Expression In Cope's Gray Treefrog (Hyla Chrysoscelis), Dalal Nouruldeen Felemban

Browse all Theses and Dissertations

In sub-freezing temperatures, cerebrospinal fluid (CSF) and blood plasma within the brain of freeze-tolerant gray treefrogs, Hyla chrysoscelis, are likely to freeze. We hypothesized that this would challenge blood-brain barrier (BBB) integrity and volume regulation for cells in the brain. Our first hypothesis, tested as cerebral Evans blue permeability, was not supported; BBB integrity appeared uncompromised by cold. Our second hypothesis, tested as changing expression of aquaporin (AQP) proteins, was partially supported. Whole-brain expression (Western blot) of AQP1 and AQP4 were unchanged by cold conditions, but AQP9 expression increased in thawed animals. AQP1 was found (immunohistochemistry) in ependymal cells, endothelial …