The circadian timing system (CTS) is an important temporal organizer controlling both physiology and behavior. Animals exposed to the microgravity environment of spaceflight exhibit alterations in both CTS function and homeostasis, including changes in body temperature regulation and metabolism, changes in the timing of physiological and behavioral functions, fragmentation of the sleep-wake cycle, and even desynchronization of some rhythmic variables from the external light- dark cycle. The investigator's previous studies have shown that exposure to hyperdynamic fields via centrifugation significantly affects both the CTS and homeostasis. The investigator also demonstrates that hypergravity alters the expression of c-Fos in the hypothalamic suprachiasmatic nucleus, a region that receives direct neural input from the retina and is thought to represent the neural pacemaker for circadian rhythm generation. This study proposes to examine the physiology of the CTS and homeostatic control systems of rats exposed to spaceflight. The first set of in- flight experiments will compare data from flight rats and ground-housed controls on heart rate and body temperature monitored telemetrically, and on activity, food intake and drinking. Separate groups of flight and control rats will be studied under conditions of normal 12 hour light/dark cycles and under constant light conditions to assess the impact of gravity changes on the CTS. A second set of in-flight experiments will assess the effects of spaceflight on c-Fos and Jun-B expression in the suprachiasmatic nucleus and other hypothalamic regions implicated in homeostatic control (a) under basal conditions, and (b) after presentation of a light pulse at a point in the light dark cycle where such intervention is known to induce phase shifting of the CTS and associated changes in c-Fos and Jun-B expression in the SCN. Data from rats sacrificed at different times in the mission will be compared with parallel data from ground- housed control rats. Pre-flight studies are proposed to optimize the conditions, procedures and protocols for the in-flight studies, and post- flight studies designed to extend the findings of the in-flight studies are also described.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL053205-03
Application #
2519441
Study Section
Special Emphasis Panel (SSS (S6))
Project Start
1995-09-30
Project End
1999-08-31
Budget Start
1997-09-30
Budget End
1998-08-31
Support Year
3
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of California Davis
Department
Neurology
Type
Schools of Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
McDonald, R B; Hoban-Higgins, T M; Ruhe, R C et al. (1999) Alterations in endogenous circadian rhythm of core temperature in senescent Fischer 344 rats. Am J Physiol 276:R824-30