Life Sciences Commons^™

Regional Specialization Of The Adult Meninges Supports Different Brain Areas And Alters With Age, Christina Ann Calabrese

Legacy Theses & Dissertations (2009 - 2024)

The meninges comprise three heterogeneous connective tissue coverings, referred to as the dura, arachnoid, and pia mater, which completely envelop the brain and spinal cord. Given the meninges’ vast coverage over the entire CNS and its unique development, I hypothesized that regional leptomeninges (arachnoid and pia mater layers combined) provide specialized support to different brain areas. During development, anterior meninges, overlying the frontal cortex, derive from neural crest cells that are ectodermal in origin. Posterior meninges, overlying the midbrain to the spinal cord, derive from a mesodermal lineage. This difference in lineage and location suggests potential functional differences between the …

An Evaluation Of Alzheimer's Disease-Related Pathology In Two Different Models Of Diabetes In Immune-Challenged Mice, Andrew Scott Murtishaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

Obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome are related disorders with wide-ranging and devastating effects that can be observed throughout the body. One important and understudied organ of damage is the brain. Clinical and epidemiological studies have found that T2DM, and more specifically hyperinsulinemia, significantly increases the risk of cognitive decline and increases the likelihood of Alzheimer’s disease (AD) and other forms of dementia in the elderly. Insulin has slightly different functions in the peripheral body than in the central nervous system and the dysregulation of these functions may contribute to the onset and progression of late-life neurodegenerative …

Exposure To Estrogenic Endocrine Disrupting Chemicals And Brain Health, Mark Preciados

FIU Electronic Theses and Dissertations

The overall objective of this dissertation was to examine exposures to the estrogenic endocrine disrupting chemicals (EEDCs), phthalates, bisphenol-A (BPA), and the metalloestrogens cadmium (Cd), arsenic (As), and manganese (Mn) in an older geriatric aged-population and examine associations with brain health. Given the evidence that EEDCs affect brain health and play a role in the development of cognitive dysfunction and neurodegenerative disease, and the constant environmental exposure through foods and everyday products has led this to becoming a great public health concern. Using a bioinformatic approach to find nuclear respiratory factor 1 (NRF1) gene targets involved in mitochondrial dysfunction, that …

Tau Aggregation, Conformational Selection, And Inhibition, Michael R. Holden

Electronic Theses and Dissertations

Tau fibrils are a pathological hallmark of over 20 neurodegenerative disorders, including Alzheimer's disease. There currently is no cure for these diseases and treatments are limited. Once Tau fibrils form in the brain, they propagate down neuronal networks, and this spreading is linked to disease progression. Studying the behavior and structure of Tau monomer and Tau aggregates therefore may give insight into methods by which the spread of Tau fibrils can be inhibited. The structures of the Tau fibrils from different diseases are thought to vary, partially giving rise to the different disease phenotypes. Tau natively binds to microtubules by …

Targeted Delivery Of A Therapeutic Protein For The Treatment Of Alzheimer's Disease, Heather Holman

Honors Undergraduate Theses

Neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease are linked to mitochondrial dysfunction and the underexpression of TOM40, a protein with chaperone-like qualities that is responsible for transporting precursor proteins into the mitochondria. Overexpression of TOM40 is reported to partially restore mitochondrial dysfunction and decrease the accumulation of neurotoxic aggregates of α-synuclein. Our goal is to develop an effective method for delivery of TOM40 protein to the brain.

Previous studies have used lentiviruses to carry TOM40 into the hippocampus of α-synuclein transgenic mice. The disadvantage of lentiviral transfection is the random insertions of the target gene into the host …

Galantamine's Deconstruction In The Quest Of A Pam Pharmacophore, Malaika Argade

Theses and Dissertations

Alzheimer’s disease is a progressive neurodegenerative disorder generally affecting people above the age of 65 years. Even though the pathophysiological hallmarks of AD were established more than a hundred years ago, there is yet to be a drug that can stop its characteristic neuronal damage. Of the five currently FDA-approved drugs, galantamine has a unique mechanism of action. Apart from being an AChE inhibitor, galantamine can effectively potentiate (positive allosteric modulator) the effect of agonists at nAChRs at concentrations lower than those required for its action as an AChE inhibitor. Perhaps the clinical benefits observed with galantamine are associated mainly …