South Carolina Space Grant Consortium REU Program

Summer 2005

Title of Project: Development of Dietary and Behavioral Countermeasures to Anorexia Associated with Space Adaptation Syndrome (SAS) and Long Term Space Travel (LTST) using Human Subjects and the Rat Anti-Orthostatic Tail Suspension Model (RATSM).

Principal Investigators: Stacey R. Hettes, Ph.D, Department of Biology

George R. Davis, Jr., Ph.D, Department of Biology

Co-Investigator:

Institution of Higher Education: WoffordCollege

Address: 429 North Church St.

Spartanburg, SC 29303

Contact Information:tel: 864-597-4659fax: 864-597-4629

Total Funds Requested: $ 44,959.40

By signing and submitting this proposal, the signatories are certifying that the institution and the proposed project are in compliance with all applicable Federal and State laws and regulations. The signatories also agree to allow the SC Space Grant Consortium to issue news releases if the project is selected.

Signature(s) of All investigators(s):

Stacey R. Hettes, Ph.D.

George R. Davis, Jr., Ph.D.

Signature of Authorized Fiscal Agent:

Robert L. Keasler, Jr., Treasurer & CFO

Signature of Campus Director:

Angela B. Shiflet, Ph.D.

2. Contact Information for Principal Investigators

Program Director/ Co- Principal Investigator:

Stacey R. Hettes, Ph.D., Assistant Professor of Biology

Address:WoffordCollege

Department of Biology

RMSC W203A

249 North Church St.

Spartanburg, SC 29303

Telephone: 864-597-4659

Fax: 864-597-4629

email:

Co- Principal Investigator:

George R. Davis, Jr., Ph.D., Professor of Biology

Address:WoffordCollege

Department of Biology

RMSC W203E

249 North Church St.

Spartanburg, SC 29303

Telephone: 864-597-4621

Fax: 864-597-4629

email:

3. Project Summary:

As NASA is making plans to return humans to the moon and then to Mars, it becomes more critical than ever to address the issues responsible for the loss of appetite and body mass experienced by space travelers. Conditions in space (microgravity, altered diurnal cycles, loss of appetite, etc.) clearly have a negative impact on the nutrient consumption and over all health of astronauts. The co-PIs for this REU will guide four undergraduates, selected on the basis of their enthusiasm for the research topic and their inclination toward a career in NASA-related research, in the design and completion of experiments, we will investigate factors that affect food intake in human subjects and in laboratory rats under conditions of simulated microgravity and orbit-like dark/light cycles. Our experiments, designed with the collaboration of the REU students and in consultation with the Advanced Food Technology (AFT) team at the Johnson Space Center, will focus on ways to manipulate the sensory qualities of food and the presentation order of various foods such that food intake is maximized. The ultimate goal of our research is to allow us to make recommendations to NASA’s AFT team regarding modifications of mission menus that will promote food consumption as a countermeasure to the anorexia associated with space flight.

Students who participate in this research will experience the excitement of conducting research with real-world implications. They will become proficient in reading the relevant literature, designing carefully controlled experiments during the spring, and completing those experiments over a 10 week summer residential experience that will include a trip to the JohnsonSpaceCenter in Houston, TX to meet with the AFT team and use some of that lab’s specialized instrumentation. Students will be instructed on the use of the appropriate statistical analyses that will permit them to draw conclusions that can be presented at local, state, regional, and/or national conferences. In the process, students will work with a rodent model that simulates microgravity to investigate a topic for which that model has not yet been employed, will be stimulated by the challenges of mastering rodent brain surgery, will learn of the myriad physiological challenges imposed by space flight, will see how teamwork is essential for mission success, will experience first-hand the exhilaration of discovery, and the satisfaction derived from presenting their results at a scientific conference.

NASA is charged to lead the way into space, but another of NASA’s missions is to improve the quality of life here on Earth. Because our studies address factors that regulate food consumption, our experimental results will very likely have implications for humans who remain Earth-bound as well. Students will be directed to think about how their findings might be used to manipulate the diet of humans so as to reduce over-consumption that leads to obesity. With the aid of this REU grant and the equipment it would provide to simulate microgravity in laboratory rats, the Biology Department at Wofford College will be able to continue research on the neural basis of feeding behavior in research courses taught each semester by the PI’s, thus exposing a larger pool of prospective NASA scientists to the excitement of research.

4. Project Description

List of Commonly Used Abbreviations:

AFT- Advanced Food Technologies

JSC-JohnsonSpaceCenter

LTST- Long Term Space Travel

RATSM- rat anti-orthostatic tail suspension model

SAS- Space Adaptation Syndrome

SCSGC- South Carolina Space Grant Consortium

SSS- Sensory Specific Satiety

4 A. Overview

Objectives of the Proposed REU Site

The objectives of the REU site are sevenfold. First, we wish to engage students in stimulating scientific inquiry such that the experience will encourage them to seek careers in research, especially in areas that are supported by and in support of NASA. The proposed research will be conducted on the campus of Wofford College and include travel to the Johnson Space Center (JSC) in Houston, TX to collaborate with Dr. Michelle Perchonok, Director of NASA’s Advanced Human Support Technology Program’s Advanced Food Technologies (AFT) team. AFT’s Food Systems Engineering Facility is the laboratory responsible for astronaut menu, food, and package research and development. Second, we want to establish a continuing relationship with NASA personnel. Drs. Hettes and Davis visited the AFT team at JSC where we became more familiar with the demands placed upon those responsible for providing for the dietary and health needs of astronauts engaged in LTST. We believe that our proposed research would be useful to AFT whose mission is to ensure the nutritional, psychological, safety, and acceptability requirements of the food supply for astronauts during space travel28. Each of our research objectives is aimed at meeting NASA’s requirements for adequate nutrition and safety and will take into consideration aspects such as convenience, eating pleasure, and space mission constraints of mass, power, volume, reliability, and crew time requirements 6,19, 21,22.

Third, we hope to enhance the quality and visibility of research currently underway at WoffordCollege by collaborating with NASA. WoffordCollege has made a firm commitment to providing undergraduate research opportunities as indicated elsewhere in the proposal, and we hope to honor that commitment by obtaining extramural funding to support these endeavors. Fourth, we hope to promote diversity on Wofford’s campus. The student body at WoffordCollege is fairly homogenous in that it consists mainly of relatively affluent Caucasians who have excelled in high school. For our REU site, we would seek highly qualified students from other institutions within SC and the Virgin Islands with preference given to minorities and women. We would also promote diversity from within by recruiting among our exceptional female and minority students.

Fifth, we want to recruit talented and capable students from throughout South Carolina and the Virgin Islands to consider research as a career. We believe WoffordCollege to be a central locus of such individuals. Fifty-seven percent of this year’s freshman class graduated in the top 10% of their high school class. Approximately one-half of the entering freshman class indicates an interest in pursuing a degree in Biology in anticipation of a career in medicine or dentistry. Because the REU research conducted during the summer would be expanded into both academic semesters at no additional expense to SCSGC, the impact of the REU would be greatly enlarged and more likely to attract talented students to NASA careers. Sixth, to bolster the impact of exposing Wofford students to NASA-related research, we hope to acquire equipment (specifically rat cages and surgical instruments) to be used in microgravity and olfactory bulbectomy experiments. Such equipment would be used year-round in many projects in which the rat model is employed in research courses for undergraduates (typical enrollment = 30 students per year). Finally, we wish to be competitive with research opportunities outside of the state that recruit heavily among Wofford students for summer research programs. Thus we hope to entice our best students to stay on campus during the summer by providing the opportunity for paid research positions.

Connection to NASA’s Mission

On January 14, 2004 NASA’s Mission objectives entered a new phase with President George W. Bush’s articulation of the emphasis toward manned deep-space exploration including extended habitation of Lunar and Martian outposts. This proclamation has resulted in a dramatic restructuring and retooling of NASA missions, including the mission of NASA’s AFT team59. With the re-emphasis on LTST, AFT’s mission takes on a new set of challenges. Historically, NASA’s space exploration missions have been hampered by astronauts’ experience of Space Adaptation Syndrome (SAS), micro-gravity related anorexia, and the psychological effects of decreased palatability, and decreased acceptability of food during LTST9,21,28,40,53. Although many postulates for the physiological etiologies of these hazardous nutritional and behavioral deficits have been investigated, relatively few nutritional, dietary, and behavioral countermeasures have been proposed as remedies 8,9,27,57. Our aim is to develop such countermeasures realizing that sustaining the health of the astronauts is paramount to the success of LTST and establishment of Lunar and Martian outposts.

As always, one aspect of NASA’s mission remains to improve the quality of life on Earth. In relation to health and feeding behavior, the difficulties encountered on Earth are the opposite of those observed in space. Industrial and developing nations are experiencing epidemic increases in obesity the treatment of which costs billions of dollars annually50,56. Interestingly, we hypothesize that over-consumption on Earth and anorexia in space may both be treated by understanding the role that sensory qualities of food play in our drive to eat. A physiological and behavioral understanding of this relationship may be the first step in positively or negatively manipulating the desire to eat by employing dietary, nutritional, and behavioral countermeasures.

Organizational Structure and Time Table*

* A detailed timetable covering the entire REU is included as a supplement at the end of Section 4: Project Description.

To achieve our objectives, we will recruit students via activities described in detail elsewhere during February of 2005. Dr. Davis will develop a webpage providing detailed information of the anticipated activities for our REU site. Selected students will attend a weekend organizational workshop in April 2005. At that time students will form two teams that will be guided in the development of 3 experimental protocols addressing our central questions. Each team will be lead by one of the co-PIs, Drs. Davis and Hettes. Dr. Hettes will serve as program director and thus will be responsible for overseeing all aspects of scheduling, recording, and reporting. With our advance preparations, we anticipate being able to begin experiments on the first day of the Summer 2005 session which will provide ample time over the 10 week session for completion of several experiments. A detailed account of our research plans is provided below. We will then follow up with our REU students during Fall 2005 to prepare for presentation(s) at scientific meetings and compile reports for SCSGC on our accomplishments.

Institutional Commitment to REU

We are fortunate that our REU site will have exclusive full-time use of 3 laboratories totaling approximately 2500 square feet. In 2003, WoffordCollege completed renovation of a state of the art science building including a 1000+ square foot Animal Housing and Experimentation Facility that we share with the Psychology Department. Our experimental protocol will be approved by WoffordCollege's Institutional Animal Care and Use Committee during Spring 2005 and Wofford will provide veterinary supervision of experimental animals. This generous demonstration of Wofford’s commitment to undergraduate research is augmented by the fact that Dr. Davis and Dr. Hettes will have no college or departmental obligations during Summer 2005 and thus will devote 100% of their time to the REU. Students housed on campus will enjoy the benefits of Wofford’s commitment to providing a comfortable living environment for its students. Students will have access to the library, computer labs, athletic center, and student recreation center while on campus. Student dormitory rooms have broadband internet, Wofford intranet, telephone, and cable TV access.

Extended impact of the REU

We fully expect that research conducted by the REU team will lead to additional experiments to be conducted by students enrolled in Introductory (Bio 250) and Advanced Research (Bio 450) courses during the fall and spring semesters of 2005 and 2006. Presently, the research conducted by students in these courses centers on the neural control of feeding behavior using the rat as a model system. With the acquisition of special cages used to simulate microgravity, our experiments in these semester-long research courses can easily be extended to address how feeding behaviors are altered under conditions of simulated microgravity. Therefore, the College will provide some travel money for faculty and Wofford REU students to present NASA-related research at local, state, regional, and/or national meetings. In addition, the college Business Office will manage all financial transactions. Thus a SCSGC three month commitment will, in reality, provide one year of focused research effort on the part of the students and multiple years on the part of the investigators.

4 B. Research Questions and NASA Ties.

Question 1: How can astronauts be encouraged to eat despite an appetite that is drastically reduced during Space Adaptation Syndrome (SAS) and remains diminished throughout a mission?

Astronauts experience a myriad of environmental and physiological changes during their time in space39,40,55. The most intense discomfort occurs during the first two days of space flight as SAS22. The symptoms of SAS (nausea, lethargy, reduced appetite, cephalad shifts in body fluids, etc.) preclude the scheduling of critical mission work during the first few days of any mission. Even after the initial discomfort of SAS, physiological disturbances persist and are manifested as reduced appetite, weight loss, and a reduction in bone density49,58. NASA’s concern regarding micro-gravity related anorexia, decreased palatability, and decreased acceptability of food during long-term space travel has been well documented6,21. The mission of NASA’s AFT team is to address nutritional, psychological, safety, and acceptability requirements of the food supply for astronauts during long-term space travel28. Studies on feeding behavior are also justified based on NASA’s mission to improve the quality of life on Earth. Thus, the knowledge we gain as we investigate the disturbances in feeding that accompany microgravity may lead to a fuller understanding of the neural disturbances responsible for obesity, anorexia, and bulimia on Earth as well. Therefore, it is critically important to understand those factors that affect appetite and feeding behavior in humans, both in normal gravity and in microgravity.

Appetite is influenced by the nature of the food consumed20,45. Astronauts indicate that a varied diet is important21, but variety is necessarily restricted by the need to simplify food preparation during a mission and to minimize mass and packaging. Thus, astronauts on longer missions subsist on a diet that repeats every 8 days, and in fact incorporates very little variation in the menu selections, especially for the breakfast meal28. Consequently, appetite and food consumption are reduced41.

Factors such as aroma, taste and texture affect a person’s intake of food to a greater extent than macronutrient content20,45,54. When satiated on one food, one tends not to consume more of that food, but will consume a different more palatable food. This phenomenon is known as sensory-specific satiety (SSS) and has been documented in humans, non-human primates, and laboratory rats1,3,17,26,30-37. By changing one aspect of a food item such as its texture, it may be possible to promote additional intake of that food. Therefore, we propose to determine whether it is possible to stimulate food intake of an entrée by varying the sensory qualities of an “appetizer.” The goal is to increase food intake by introducing variety in the diet, which may be achieved by varying the characteristics of food items (such as texture) and the sequence in which various food items are consumed.

Given the restricted menu of astronauts, we propose to use food items normally included in the mission diet (to be decided upon during consultation with the AFT team) to determine if food intake can be enhanced by altering the sequence in which the items are consumed. For instance, one might test whether consumption of a “crunchy” food item increases the consumption of a second food item of a different texture. These experiments will be conducted on human subjects as described more completely in the section on “Nature of Student Activities.”

Question 2: How can the sensory qualities of food be manipulated to encourage consumption, especially in microgravity?

Prior to a mission, astronauts self-select their in-flight menus, yet they typically report that the menu seems less appealing during a mission and thus consumption is reduced21. Foods acceptable at 1G are deemed less desirable in microgravity. Therefore, it is important to understand the mechanisms by which microgravity might reduce palatability of food8. To address such questions on Earth, it is necessary to have a model in which microgravity can be simulated13, 51,57. Such a model exists for laboratory rats. In the rat anti-orthostatic tail suspension model (RATSM) a rat is suspended by the tail at 30-45o angle such that hind limbs are unloaded24,25. This manipulation replicates many of the attributes of space flight in humans, including cephalad fluid shifts, muscle atrophy, changes in energy expenditure, hormone levels, and a reduction in bone density 4,5,7,13,29,51,52,58. The model has been thoroughly validated; over 800 publications to date have employed RATSM24,51. A number of these studies report a reduction in food intake and a decrease in body mass9,49,51. However, to our knowledge, none of these studies have specifically addressed how the taste, smell, or texture of foods may be manipulated to promote food intake.