As humans, we have constant physiological parameters that guide our behaviors – such as sleep – with circadian rhythms dominating these patterns. Circadian rhythms are those that persist in constant conditions with a period close to 24 hours. In space, the loss of a 24-hr day/night cycle affects the ability of astronauts to sleep, and in the case of long-duration flights, can lead to internal desynchronization, which has profound effects on an astronauts capability to perform (mentally and physically) and to remain healthy. This animal study by Dr. Gianluca Tosini will test if melatonin injection and exposure to brief pulses of light can prevent internal desynchronization, and seeks to understand the mechanisms responsible.
Overview
Preventing Desynchronization of the Circadian System in Long-Term Spaceflight
Principal Investigator:
Gianluca Tosini, Ph.D.
Organization:
Morehouse School of Medicine
Technical Summary
Many biochemical, physiological and behavioral parameters exhibited by organisms show daily fluctuations, and most of these daily rhythms persist in constant conditions, thus, demonstrating that they are driven by endogenous oscillators. The rhythms that persist in constant conditions with a period close to 24 hours are called circadian rhythms. One of the most important aspects of spaceflight is the absence of geophysical 24 hour cycles, which, of course, affects the overall temporal organization of the organisms. In the case of long-duration manned spaceflight, it is crucial to understand how the whole circadian system would react and behave in such circumstances.
We discovered that exposing rats to constant dim light for 60 days may induce spontaneous internal desynchronization in a few animals. In the present research project, we further examined this phenomenon by investigating the physiological consequences of spontaneous internal desynchronization in order to develop countermeasures to obviate the occurrence of internal desynchronization in animals exposed to constant dim light. Spontaneous internal desynchronization has profound effects on the capability of the organisms to perform (mentally and physically) and to remain healthy.
Recent studies have shown that a subset of retinal ganglion cells (RGCs) innervating the suprachiasmatic nucleus (SCN) is directly photosensitive and able to convert electromagnetic radiation into neural signals. Melanopsin, a photopigment based on vitamin A, was found in these RGCs and is the strongest candidate for the circadian photopigment within these cells. The spectral sensitivity of these RGCs peak around 474 nanometer (nm).
It is now believed that these RGCs provide the main light input to the circadian clock. In the last year of funding, we have developed a series of light blue narrow-band light-emitting diodes (LEDs) with an emission peak at 476 nm that should be very effective in stimulating the photosensitive RGCs. Indeed, our preliminary data indicate that these LEDs may be a valid countermeasure to prevent dysfunctions of the circadian system that may occur in the spaceflight.
Earth Applications
Our project has provided important data on the physiological mechanisms that are involved in the maintenance of the synchronization among the different circadian oscillators. The data that will be generated by this project will allow the design of specific treatments (pharmacological or environmental) that will prevent the desynchronization of the circadian system. Such treatments will then be employed in the treatment of circadian dysfunctions due to a pathological or environmental condition that may affect some individuals. Furthermore, the LEDs that we have developed may be useful in the treatment of several pathologies such as seasonal affective disorders and sleep disorders.
This project's funding ended in 2007