Medical Pharmacology Commons^™

Targeting Astrocytes Ameliorates Neurologic Changes In A Mouse Model Of Alzheimer's Disease, Jennifer L. Furman, Diana M. Sama, John C. Gant, Tina L. Beckett, M. Paul Murphy, Adam D. Bachstetter, Linda J. Van Eldik, Christopher M. Norris

Pharmacology and Nutritional Sciences Faculty Publications

Astrocytes are the most abundant cell type in the brain and play a critical role in maintaining healthy nervous tissue. In Alzheimer's disease (AD) and most other neurodegenerative disorders, many astrocytes convert to a chronically "activated" phenotype characterized by morphologic and biochemical changes that appear to compromise protective properties and/or promote harmful neuroinflammatory processes. Activated astrocytes emerge early in the course of AD and become increasingly prominent as clinical and pathological symptoms progress, but few studies have tested the potential of astrocyte-targeted therapeutics in an intact animal model of AD. Here, we used adeno-associated virus (AAV) vectors containing the astrocyte-specific …

Sterol Lipid Metabolism In Down Syndrome Revisited: Down Syndrome Is Associated With A Selective Reduction In Serum Brassicasterol Levels, Gavin Tansley, Daniel T. Holmes, Dieter Lütjohann, Elizabeth Head, Cheryl L. Wellington

Pharmacology and Nutritional Sciences Faculty Publications

Over the past 15 years, insights into sterol metabolism have improved our understanding of the relationship between lipids and common conditions such as atherosclerosis and Alzheimer's Disease (AD). A better understanding of sterol lipid metabolism in individuals with Down Syndrome (DS) may help elucidate how this population's unique metabolic characteristics influence their risks for atherosclerosis and AD. To revisit the question of whether sterol lipid parameters may be altered in DS subjects, we performed a pilot study to assess traditional serum sterol lipids and lipoproteins, as well as markers of sterol biosynthesis, metabolites, and plant sterols in 20 subjects with …

Aging And Down Syndrome, Elizabeth Head, Wayne Silverman, David Patterson, Ira T. Lott

Pharmacology and Nutritional Sciences Faculty Publications

No abstract provided.

Sr-A Ligand And M-Csf Dynamically Regulate Sr-A Expression And Function In Primary Macrophages Via P38 Mapk Activation, Dejan Nikolic, Lindsay Calderon, Liqin Du, Steven R. Post

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: Inflammation is characterized by dynamic changes in the expression of cytokines, such as M-CSF, and modifications of lipids and proteins that result in the formation of ligands for Class A Scavenger Receptors (SR-A). These changes are associated with altered SR-A expression in macrophages; however, the intracellular signal pathways involved and the extent to which SR-A ligands regulate SR-A expression are not well defined. To address these questions, SR-A expression and function were examined in resident mouse peritoneal macrophages incubated with M-CSF or the selective SR-A ligand acetylated-LDL (AcLDL).

RESULTS: M-CSF increased SR-A expression and function, and required the specific …

Borderline Personality Disorder: An Overview Of History, Diagnosis And Treatment In Adolescents, Linah Al-Alem, Hatim A. Omar

Pharmacology and Nutritional Sciences Faculty Publications

Borderline personality disorder (BPD) is a cluster B personality disorder. It is characterized by erratic behaviors, emotional instability and one of its hallmarks is self injurious behavior, which starts in adolescence. Patients with BPD are difficult to treat, most have a history of child sexual abuse, about a quarter present with sexual abuse from a caretaker. Although personality disorders are diagnosed only in adults, BPD manifests itself in adolescence in the form of uncontrollable anger, self mutilations, dissociation and other such behaviors. Hence, there is a growing number of scientists discussing the possibility of diagnosing BPD in adolescents. Here, we …

Expansion Of The Calcium Hypothesis Of Brain Aging And Alzheimer's Disease: Minding The Store, Olivier Thibault, John C. Gant, Philip W. Landfield

Pharmacology and Nutritional Sciences Faculty Publications

Evidence accumulated over more than two decades has implicated Ca2+ dysregulation in brain aging and Alzheimer's disease (AD), giving rise to the Ca2+ hypothesis of brain aging and dementia. Electrophysiological, imaging, and behavioral studies in hippocampal or cortical neurons of rodents and rabbits have revealed aging-related increases in the slow afterhyperpolarization, Ca2+ spikes and currents, Ca2+transients, and L-type voltage-gated Ca2+ channel (L-VGCC) activity. Several of these changes have been associated with age-related deficits in learning or memory. Consequently, one version of the Ca2+ hypothesis has been that increased L-VGCC activity drives many of the other Ca2+-related biomarkers of hippocampal aging. …