Behavioral Neurobiology Commons^™

All The Rage: Assessing The Age/Rage Signaling Pathway’S Effects On Healthspan And The Physiological Processes Of Aging, Brandon Ashmore

Honors Theses

Advanced glycation end products (AGEs) are protein, lipid, or nucleotide molecules that have been combined with sugars through nonenzymatic, irreversible glycation and oxidation reactions. Their accumulation in the body has been associated with the natural aging process and a wide range of pathologies, including chronic inflammation, sustained oxidative stress, diabetes, neurodegenerative diseases, atherosclerosis, and cancer. Their interaction with the receptor for advanced glycation end products (RAGE) has been linked to several proinflammatory signaling pathways associated with neurotoxicity and vascular lesions. While some research has been done on the possible health benefits of RAGE inhibition to extend lifespan, our study hopes …

Behavioral Insights Into Nociceptor Function: A Systematic Approach To Understanding Postsurgical And Neuropathic Pain Mechanisms In Rats, Max Odem

Dissertations & Theses (Open Access)

Postsurgical and neuropathic pain are each clinically common, and often associated with ongoing pain. Ongoing pain has been linked to ongoing activity (OA) in human C-fiber nociceptors. Preclinical studies using rodent neuropathic models have concentrated on allodynia driven by OA generated in non-nociceptive Aβ fibers, but little attention has been paid to postsurgical pain in sham controls or to C-fiber nociceptor OA promoting ongoing pain.

Operant assays that reveal negative motivational and cognitive aspects of voluntary pain-related behavior may be particularly sensitive to pain-related alterations. In the mechanical conflict (MC) test, rodents can freely choose to escape from a brightly …

White Matter Inflammation And Executive Dysfunction: Implications For Alzheimer Disease And Vascular Cognitive Impairment, Alexander Levit

Electronic Thesis and Dissertation Repository

White matter integrity is crucial to healthy executive function, the cognitive domain that enables functional independence. However, in the ageing brain, white matter is highly vulnerable. White matter inflammation increases with age and Alzheimer disease (AD), which disrupts the normal function of white matter. This may contribute to executive dysfunction, but the relationship between white matter inflammation and executive function has not been directly evaluated in ageing nor AD. White matter is also particularly vulnerable to cerebrovascular disease, corresponding with the common presentation of executive dysfunction in vascular cognitive impairment (VCI). Thus, white matter may be an important substrate by …

Curcumin Inhibits The Ikk:Nf-Kappa B Pathway In Neural Fear Circuits, Miguel A. Briones

Dissertations, Theses, and Capstone Projects

The study of how the brain acquires fearful memories has attracted considerable experimental attention, due in part to the promise of discovering novel therapeutic approaches for psychiatric disorders that are characterized by unusually strong and persistent traumatic memories. In recent years, extensive research has focused on studying the neural and molecular mechanisms by which fear memories are acquired, stored, and retrieved in the brain. Once acquired, fear memories may be attenuated using one of 2 procedures: 1) fear extinction, which involves repeated presentation of the fear-arousing stimulus in the absence of an aversive consequence, or 2) interference with the reconsolidation …

Complexities Of Chronic Opioid Exposure, Maciej Gonek

Theses and Dissertations

Studies on repeated exposure to opioids have been carried out for decades yet the mechanisms for certain phenomena such as tolerance are still not fully understood. Furthermore, different medications, such as frequently prescribed benzodiazepines, or different disease states, such as HIV, have their own effects and interactions with chronic opioid exposure that are not fully understood. The overall objective of this dissertation was to investigate the complexities of chronic opioid exposure and how different disease states and medications may modulate the effects of chronic opioids. Our findings demonstrate that the administration of diazepam, at doses that are not antinociceptive or …

Injury Establishes Constitutive Μ-Opioid Receptor Activity Leading To Lasting Endogenous Analgesia And Dependence, Gregory F. Corder

Theses and Dissertations--Physiology

Injury causes increased pain sensation in humans and animals but the mechanisms underlying the emergence of persistent pathological pain states, which arise in the absence of on-going physical damage, are unclear. Therefore, elucidating the physiological regulation of such intractable pain is of exceptional biomedical importance. It is well known that endogenous activation of µ-opioid receptors (MORs) provides relief from acute pain but the consequences of prolonged endogenous opioidergic signaling have not been considered. Here we test the hypothesis that the intrinsic mechanisms of MOR signaling promote pathological sensitization of pain circuits in the spinal cord. We found that tissue inflammation …

Post-Traumatic Sleep Following Diffuse Traumatic Brain Injury, Rachel K. Rowe

Theses and Dissertations--Neuroscience

Traumatic brain injury (TBI) is a major cause of death and disability throughout the world with few pharmacological treatments available for individuals who suffer from neurological morbidities associated with TBI. Cellular and molecular pathological processes initiated at the time of injury develop into neurological impairments, with chronic sleep disorders (insomnia, hypersomnolence) being among the somatic, cognitive and emotional neurological impairments. Immediately post-injury, TBI patients report excessive daytime sleepiness, however, discordant opinions suggest that individuals should not be allowed to sleep or should be frequently awoken following brain injury. To provide adequate medical care, it is imperative to understand the role …

Neurosteroid-Mediated Regulation Of Brain Innate Immunity In Hiv/Aids: Dhea-S Suppresses Neurovirulence, Amber Paul, Ferdinand G. Maingat, Maria J. Polyak, Pornpun Vivithanaporn, Farshid Noorbakhsh, Samir Ahboucha, Glen B. Baker, Keir Pearson, Christopher Power

Publications

Neurosteroids are cholesterol-derived molecules synthesized within the brain, which exert trophic and protective actions. Infection by human and feline immunodeficiency viruses (HIV and FIV, respectively) causes neuroinflammation and neurodegeneration, leading to neurological deficits. Secretion of neuroinflammatory host and viral factors by glia and infiltrating leukocytes mediates the principal neuropathogenic mechanisms during, although the effect of neurosteroids on these processes is unknown. We investigated the interactions between neurosteroid mediated effects and lentivirus infection outcomes. Analyses of HIV-infected uninfected human brains disclosed a reduction in neurosteroid synthesis enzyme expression. Human neurons exposed to supernatants from HIV macrophages exhibited suppressed enzyme expression without …