The ability of restricted temporal windows of food availability to synchronize behavioral and physiological circadian rhythms to is well documented. These changes in circadian rhythms are thought to be sub served by a food-entrainable oscillator (FEO) in the circadian timing system (CTS) that is independent of the light entrainable pacemaker, the suprachiasmatic nucleus (SCN). The (neuro)anatomical locus and molecular mechanisms of the FEO have, however, remained unresolved. Recent work by the Saper laboratory has identified the dorsomedial hypothalamic nucleus (DMH) as a critical structure for the expression of food entrained circadian rhythms, supporting the concept that the DMH may function as a FEO. The present proposal is aimed at the further characterization of: 1) the molecular mechanism by which the DMH generates circadian rhythms; 2) the role of the DMH in coordinating peripheral tissue oscillators to restricted feeding; and 3) the molecular basis of DMH entrainment. By understanding the molecular-basis of the DMH and how the DMH modulates CTS function, therapeutic strategies and diagnostic approaches may be developed to alleviate circadian, sleep-wake and, possibly, metabolic disorders with a CTS basis. Understanding the (neuro)-biology of the FEO-CTS interrelationship may have significant clinical applications for 1) patients receiving continuous, as opposed to circadian optimized, parenteral nutrition; and 2) scheduling food- and light-exposure timing for minimizing desynchrony, e.g., jet-lag. By understanding the neuroanatomical and molecular basis of the FEO and how the FEO modulates CTS function, therapeutic strategies and diagnostic approaches may be developed to alleviate circadian, sleep-wake, and, likely, metabolic disorders with a FEO-CTS basis. ? ? ?
|Fuller, Patrick M; Lu, Jun; Saper, Clifford B (2008) Differential rescue of light- and food-entrainable circadian rhythms. Science 320:1074-7|