Sonsoles de Lacalle - US grants

DESCRIPTION: (Verbatim from the Applicant's Abstract) In these studies we propose to examine the ability of estrogen to stimulate the compensatory sprouting response of the cholinergic system in an area that is first and most profoundly affected in Alzheimer's disease (AD), the entorhinal cortex (EC). Several reports have described increased synaptic sprouting in response to estrogen, and have implicated this hormone in the upregulation of cholinergic function in the basal forebrain. Based on these studies and on our own results, we hypothesize that estrogen may induce cholinergic sprouting and reactive synaptogenesis in response to cell loss, and perhaps bring about some degree of functional recovery. The basic premise of the proposed experimentation is that estrogen has a neuroprotective effect that restores and prolongs the function of damaged basal forebrain cholinergic neurons. Male and female Fisher 344 rats, young (3 months old) and aged (24 months old), both gonadectomized and intact, will receive a lesion that mimics the cortical cholinergic denervation in AD. Unilateral lesions (allowing for the contralateral side to act as an internal control) will be produced in the nucleus of the horizontal limb of the diagonal band of Broca (HDB) using 192 IgG-saporin immunotoxin complex as the lesioning tool. This immunotoxin specifically targets cholinergic neurons. Treatment with estrogen or placebo will begin four weeks after lesioning, when maximal EC denervation has occurred. For specific aim 1 we will use standard immunohistochemical techniques to measure the change in lesion-induced cholinergic sprouting in the EC that results from estrogen treatment. In specific aim 2 we will employ a modification of the Fonnum method to assay choline acetyltransferase (ChAT) activity in the same EC area. In specific aim 3 we will examine the regenerative effects of estrogen on surviving basal forebrain cholinergic neurons by semi-quantitative RT/PCR analysis of changes in the mRNA expression of two cholinergic markers, the synthetic enzyme ChAT and the vesicular acetylcholine transporter (VAChT). Finally, in specific aim 4 we will test the hypothesis that estrogen can ameliorate lesion- and age-dependent behavioral impairments. Experimental animals will be tested before and after estrogen treatment using an odor discrimination task that is sensitive to EC damage. The resulting measures of behavior will be correlated with cortical fiber sprouting and with levels of cholinergic activity in the cortex and basal forebrain.

entorhinal cortex; choline acetyltransferase; synaptogenesis; hormone regulation /control mechanism; aging; Alzheimer's disease; estrogens; neurogenesis; physical chemical interaction; cell growth regulation; messenger RNA; tissue /cell culture; polymerase chain reaction; laboratory rat; statistics /biometry; immunocytochemistry;

DESCRIPTION (provided by applicant): California State University Los Angeles (Cal State LA), a minority institution with a long tradition of success in developing the careers of minority Americans in the biomedical sciences, proposes to establish an Honors Undergraduate Research Training Program (COR). This program seeks to foster careers in specific disciplines related to mental health, supporting capable individuals whose abilities might otherwise be lost to biobehavioral research. The goal of the program is to prepare the participants to compete successfully for entry into graduate programs leading to the Ph.D. or M.D./Ph.D. at major research institutions. Cal State LA already has a long tradition of placing students in professional schools. This new project is unique in that it would contribute to increase minority participation in research in areas related to mental health. Taking advantage of the presence of a diverse group of very productive faculty members with research interests directly related to mental health, we propose to train each year a group of eight students in those research laboratories. The participants in the COR program will experience a substantial career advancement through a specific program designed to increase their research skills and enhance their academic background in the behavioral sciences. In addition, participation in this program will integrate them into the Southern California research community; will expose them to a broad range of biobehavioral sciences and scientists; enhance their entry directly into M.D./Ph.D. or Ph.D. programs, and establish the foundation for their successful research careers in areas related to mental health.

[unreadable] DESCRIPTION (provided by applicant): This NCRR Science Education Partnership Award titled "Would you like to be a scientist? Discover Biomedical Sciences!" has two interrelated goals. On the one hand, it seeks to expose children from inner city elementary schools to the biomedical sciences, and, as a consequence, encourage them early on with the excitement of scientific discovery and health careers. On the other hand, it seeks to train science undergraduates to become good communicators of their science, involving them in bringing science - particularly health-related discoveries - to the public. To achieve these goals, we propose the following specific aims: Specific Aim 1: To create a science outreach program run by undergraduates in biomedical sciences, directed towards fourth grade students. This outreach program will have two components: A) a "reverse" science fair, modeled after the Kids Judge! Neuroscience Fairs that we have used in the past. This activity will be focused in neuroscience concepts, and will provide children with learning experiences that will establish the foundation for broad understanding of how the brain works and how brain functioning relates to behavior. B) a mentoring program between the 4th graders and the Biomedical Sciences undergraduates, whereby the college students will work with, and serve as a resource for the elementary school children for the science portion of their curriculum. Specific Aim 2: To establish a public outreach activity that will educate the general public on biomedical sciences and other health-related topics, using films with a scientific content, discussed by researcher or clinician chosen among those who can provide not only the best scientific expertise, but also a model to imitate. [unreadable] This application also addresses a critical barrier to progress in the field of minority health and health disparities, by contributing to increase the number of members of underrepresented groups that enter the biomedical workforce. There are two reasons for this. First, minority students in urban public schools often do not acquire essential academic skills necessary to pursue science careers. Second, as of today minority students do not have access to appropriate role models because underrepresented minorities account for a disproportionately low percentage of full time academic faculty (less than 4%) at US medical schools, and are less likely to hold senior academic rank even after adjusting for years as a faculty member or measures of academic productivity. Participation in our program will serve not only to increase access to science content and spur heightened interest in the children, but also this will come from students and faculty that 'talk like them and look like them', providing role models to whom the inner-city 4th graders can relate to. [unreadable] [unreadable] [unreadable]

The purpose of this Initiative to Enhance Diversity in the Biomedical Research Workforce at CSU Channel Islands is to initiate the evaluation of specific approaches to training, aimed at increasing the number of students from underrepresented groups and underserved backgrounds who obtain baccalaureate degrees in disciplines relevant to biomedical research, and pursue science and health related research careers. While it is encouraging that the US has seen an increase in the number of advanced degrees awarded to individuals from backgrounds traditionally underrepresented in the biomedical sciences, a high attrition rate has also been reported. Data on the specific elements that contribute to successful outcomes remain limited, partly due to the difficulty of identifying the multidimensional factors that influence success. Capitalizing on the results available to date from the trans-NIH Diversity Program Consortium (DPC), this proposal seeks to answer the following questions: Is it possible to motivate students to choose a career in biomedical research through specific curricular components within the constraints of a teaching-intensive institution (PUI)? To what extent a focused investment in training faculty from biomedically-relevant disciplines at PUIs can inspire and support students in the decision to pursue careers in biomedical research? We anticipate answering these questions through the following specific aims: Specific Aim 1: To design, implement and evaluate a techniques-intense summer course (the Biomedical Research Bootcamp) that will introduce students to biomedical research, using neuroscience concepts as a common thread. An age-matched group of non-participant students from the same disciplines will be recruited as comparison. We will collect data from all students before the course (baseline) and at intervals throughout their undergraduate career, and continuing 4 years beyond the end of the funding. Specific Aim 2: To design, implement, and evaluate a tenure-track faculty training program focused on curriculum development, grant writing, and mentoring (2 modules). We will recruit 24 faculty members from the relevant departments (Psychology, Health Science, Biology, Chemistry and Applied Physics), and randomly assign them to unspecific (n=8) or specific training (n=16). The comparison group will participate in the professional development activities traditionally offered by the institution. The specific training group will be assigned semi-randomly to each module, so by the end of the funding all 16 participants will have received training in both modules. All 24 participants will be evaluated before the start of the training (baseline) and throughout their progress in each module. Our proposal has been designed in collaboration with an expert team of evaluators and statisticians, skilled in test validation as well as in development of psychometric methods that take into consideration multicultural settings. We are confident that at the end of this study, CSU Channel Islands will have a better understanding of effective approaches to biomedical student engagement and mentoring, research capacity building, and faculty development. It is expected that this knowledge will allow CSU Channel Islands to exert a powerful contribution on the preparation of trainees from diverse backgrounds, helping them to succeed in biomedical research careers.