Chronic Inflammation in the Alzheimer’s Disease Brain
Dr. Ron Strohmeyer
Dr. Strohmeyer’s research interests lie in the area of chronic brain inflammation in neurodegenerative diseases, with a primary focus on Alzheimer’s disease. Chronic brain inflammation has been studied in the Alzheimer’s disease brain for nearly two decades and has resulted in extensive studies of the inflammatory proteins and toxic molecules, their effects on brain cells, and even the brain cells producing them. Less well studied have been the controls within cells that regulate these processes. Cells control their expression of proteins and molecules by carefully regulating the expression of the genes encoding them in the DNA of the cell’s nucleus. Special proteins called transcription factors work together to achieve very tightly controlled programs of gene expression.
Dr. Strohmeyer’s current research interests are in studying a transcription factor family that plays a central role in regulating several cellular programs of interest in Alzheimer’s disease. This family is known as the CCAAT/Enhancer Binding Proteins (C/EBPs) and has six members. Dr. Strohmeyer is currently focusing on studying the role of C/EBPs in regulating the expression of inflammatory genes in microglia and astrocyte cells in the brain. These two brain cell types have been shown to express C/EBPs by Dr. Strohmeyer and are expected to regulate inflammatory genes in these cells. Dr. Strohmeyer’s research objective is to show this to be the case and to determine the signals that must occur in the cell to activate C/EBPs. By conducting studies that further our understanding of these processes, we may obtain novel insights that might prove to be therapeutically useful in Alzheimer’s and other neurodegenerative diseases having an inflammatory component.
Dr. Strohmeyer’s research currently encompasses the following four detailed objectives:
- Characterizing the expression pattern of each C/EBP isoform in human brain tissue and in brain cell cultures.
- Assessing the functionality of C/EBPs in modulating the expression of cytokine, chemokine, complement, iNOS, and other inflammatory genes.
- Assessing the role of C/EBPs in glial cell activation and differentiation in response to inflammatory stimuli and * amyloid protein.
- Determining whether C/EBPs may be modulated by anti-inflammatory drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) (i.e. ibuprofen), cholesterol-lowering drugs collectively known as statins, and natural compounds such as plant-derived polyphenols.
Ecology and Conservation of Herpetofauna
Dr. John Cossel, Jr.
Dr. Cossel has had a lifelong interest in studying organisms in their natural environments and was always drawn to the “creepy crawlies” of the animal kingdom, particularly the combined taxa of amphibians and reptiles (herpetofauna). Dr. Cossel completed his biology education degree here at NNU in 1991; his masters degree also focused on biology education, and included a special video project highlighting the reptile species of the Pacific Northwest. The focus of his doctoral work shifted towards the ecology of Idaho reptiles. Specifically, he was interested in determining the impacts that the altered fire regimes and the subsequent loss of millions of acres of native shrubs may have had on reptile communities. Dr. Cossel has used these experiences to create a research environment in which students can learn about the processes of science while exploring issues of ecological and conservational importance.
Dr. Cossel’s lab has worked extensively with a sensitive species of lizard in Idaho, the Great Basin Collared Lizard (Crotaphytus bicinctores). While working with this lizard, Dr. Cossel and his students have made use of radio telemetry and global positioning systems (GPS) to determine movement patterns and home range size, habitat use, population density, thermal ecology, and assessment of techniques for spatial data collection. Recently, his lab has explored the impacts of land management practices (rock removal) on reptile communities, and two of his students (Susan Young and Peter Ott) won the Idaho Academy of Science Biology Poster competition in 2005 with their poster titled "Rock Selection of the Great Basin Collared Lizard (Crotaphytus bicinctores): Assessing Resource Competition Between Miners and Lizards." During the summer of 2005, Dr. Cossel’s lab began a collaborative project in which they are using geographical information systems (GIS) to generate computer models of the distribution of collared lizards within the state of Idaho.
Herpetofauna ecology has been the topic of a number of grants that Dr. Cossel has been awarded from various entities including the Murdock Charitable Trust, Idaho Department of Fish and Game, Idaho Army National Guard, Bureau of Land Management and the National Aeronautics and Space Administration.
Impact of Ethanol on Alcohol Dehydrogenase and Redox Regulation in Humans
Dr. Jennifer Chase
Consumption of beverage alcohol (ethanol) by humans can disrupt many normal metabolic processes. The cells of liver and other tissues must divert processing enzymes from normal functions to process ethanol, thus reducing the production of important compounds such as the vitamin A (retinol) derivative, retinoic acid. It has been hypothesized that the disruption in synthesis of retinoic acid by ethanol is an underlying cause of fetal alcohol syndrome. The main enzyme responsible for retinoic acid synthesis is alcohol dehydrogenase IV (ADH-IV), most abundant in the stomach and intestines in adults, and essential for proper fetal development. A second well-recognized impact of ethanol consumption is a decrease in the NAD+/NADH ratio, especially in the liver. Because dissociation of NADH is the rate-limiting step in the oxidation of retinol, increases in the level of NADH in the presence of ethanol could also contribute to the decrease in retinoic acid production. The significance of the two different inhibitory effects of elevated ethanol levels affecting the rate of retinoic acid synthesis has not been defined. Our goal is to develop a computer simulation model of the interactions of ethanol on the liver NAD+/NADH ratio and its impact on the retinol oxidation apparatus of the cell. In a preliminary simulation using a model consisting of just ADH-IV and a “NADH oxidase” to reform NAD+, we found that the control of the rate of retinol oxidation is distributed between ADH-IV and the “NADH oxidase,” with more control by “NADH oxidase” at higher ethanol levels.
Thus, we have quantified the importance of the cellular capacity to reoxidize NADH as a potential contributor to fetal alcohol syndrome. Validation of the model is utilizing a human ADH-IV clone. The simulation work is being expanded to other cellular types and conditions to encompass more of the ADH isoenzyme types, steps converting retinaldehyde to retinoic acid, and to expand the description of the “NADH-oxidase.” We would like to gain an understanding of the control of all reaction pathways affecting NADH levels and retinol oxidation. Such information might allow medical professionals to predict who is most likely to be adversely affected by consumption of beverage alcohol and might explain differences in response that currently confound studies on the causes of fetal alcohol syndrome and other alcohol-related diseases.