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Fiscal Year:
FY 2007
Task Last Updated:
02/01/2008
PI Name:
Tosini, Gianluca
Project Title:
Preventing Desynchronization of the Circadian System in Long-Term Space Flight
Division Name:
Human Research
Program/Discipline:
NSBRI Teams
Element/Subdiscipline:
Human Performance Factors, Sleep, and Chronobiology Team
Joint Agency Name:
Human Research Program Elements:
None
Human Research Program Risks::
None
Human Research Program Gaps:
None
PI Email:
tosinig@msm.edu
Fax:
404-752-1041
PI Organization Type:
UNIVERSITY
Phone:
404-756-5214
Organization Name:
Morehouse School of Medicine
PI Address 1:
720 Westview Dr. S.W.
PI Address 2:
PI Web Page:
http://www.msm.edu/neurohomepage/tosini.htm
City:
Atlanta
State:
GA
Zip Code:
30310-1495
Congressional District:
5
Comments:
Project Type:
GROUND
Solicitation:
2003 Biomedical Research & Countermeasures 03-OBPR-04
Start Date:
09/01/2004
End Date:
08/31/2007
No. of Post Docs:
1
No. of PhD Degrees:
0
No. of PhD Candidates:
0
No. of Master' Degrees:
0
No. of Master's Candidates:
0
No. of Bachelor's Degrees:
1
No. of Bachelor's Candidates:
0
Monitoring Center:
NSBRI
Contact Monitor:
Contact Phone:
Contact Email:
Flight Program:
Flight Assignment:
Key Personnel Changes/Previous PI:
COI Name (Institution):
Fukuhara, Chiaki (
Morehouse School of Medicine )
Grant/Contract No.:
NCC 9-58-HPF00407
Performance Goal No.:
Performance Goal Text:
Task Description:
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 the most important aspects of space flight is the absence of geophysical 24-h cycles, which, of course, affects the overall temporal organization of the organisms. In the case of long-duration manned space flight, 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 proposal we further examined this phenomenon by investigating the physiological consequences of spontaneous internal desynchronization and 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 SCN are 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 RGC peak around 474 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 retinal ganglion cells. Indeed, our preliminary data indicate that these LEDs may be a valid countermeasure to prevent disfunctions of the circadian system that may occur in the space flight.
Research Impact/Earth Benefits:
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 develop may be useful in the treatment of several pathologies such as seasonal affective disorders and sleep disorders.
Task Progress:
During the last year we have tested the efficacy of our new blue narrow-band light-emitting diodes (LEDs). Our data indicate that these LEDs are very effective in modulating some circadian parameters (melatonin suppression and phase-shift of the locomotor activity). Preliminary data support the safety of these LEDs.
Bibliography Type:
Description: (Last Updated: 02/21/2008) Show Cumulative Bibliography Listing
Articles in Peer-reviewed Journals
Tosini G, Davidson AJ, Fukuhara C, Kasamatsu M, Castanon-Cervantes O. "Localization of a circadian clock in mammalian photoreceptors." FASEB J. 2007 Dec;21(14):3866-71. Epub 2007 Jul 9.
PMID: 17621597 , Dec-2007
Articles in Peer-reviewed Journals
Tosini G, Kasamatsu M, Sakamoto K. "Clock gene expression in the rat retina: effects of lighting conditions and photoreceptor degeneration." Brain Res. 2007 Jul 23;1159:134-40. PMID: 17560558 , Jul-2007
Articles in Peer-reviewed Journals
Tosini G, Aguzzi J, Bullock NM, Liu C, Kasamatsu M. "Effect of photoreceptor degeneration on circadian photoreception and free-running period in the Royal College of Surgeons rat." Brain Res. 2007 May 7;1148:76-82. PMID: 17382912 , May-2007
Awards
Tosini G. "Selected as 2008 Copernicus Visiting Scientist by University of Ferrara, August 2007." Aug-2007
Papers from Meeting Proceedings
Nicol D, Li N, Park E- U, Tosini G, Ferguson IT. "Imitating broadband diurnal light variations using solid state light light sources." 1st International Conference on Display LEDs (ICDL 2007), Seoul, Korea, Jan 31 - Feb 2, 2007.
Proceedings of the 1st International Conference on Display LEDs (ICDL 2007), Seoul, Korea, Jan 31 - Feb 2, 2007. , Feb-2007
Fiscal Year:
FY 2006
Task Last Updated:
01/08/2007
PI Name:
Tosini, Gianluca
Project Title:
Preventing Desynchronization of the Circadian System in Long-Term Space Flight
Division Name:
Human Research
Program/Discipline:
NSBRI Teams
Element/Subdiscipline:
Human Performance Factors, Sleep, and Chronobiology Team
Joint Agency Name:
Human Research Program Elements:
None
Human Research Program Risks::
None
Human Research Program Gaps:
None
PI Email:
tosinig@msm.edu
Fax:
404-752-1041
PI Organization Type:
UNIVERSITY
Phone:
404-756-5214
Organization Name:
Morehouse School of Medicine
PI Address 1:
720 Westview Dr. S.W.
PI Address 2:
PI Web Page:
http://www.msm.edu/neurohomepage/tosini.htm
City:
Atlanta
State:
GA
Zip Code:
30310-1495
Congressional District:
5
Comments:
Project Type:
GROUND
Solicitation:
2003 Biomedical Research & Countermeasures 03-OBPR-04
Start Date:
09/01/2004
End Date:
08/31/2007
No. of Post Docs:
1
No. of PhD Degrees:
0
No. of PhD Candidates:
0
No. of Master' Degrees:
0
No. of Master's Candidates:
0
No. of Bachelor's Degrees:
2
No. of Bachelor's Candidates:
1
Monitoring Center:
NSBRI
Contact Monitor:
Contact Phone:
Contact Email:
Flight Program:
Flight Assignment:
Key Personnel Changes/Previous PI:
COI Name (Institution):
Fukuhara, Chiaki (
Morehouse School of Medicine )
Grant/Contract No.:
NCC 9-58-HPF00407
Performance Goal No.:
Performance Goal Text:
Task Description:
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 the most important aspects of space flight is the absence of geophysical 24-h cycles, which, of course, affects the overall temporal organization of the organisms. In the case of long-duration manned space flight, 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 proposal we further examined this phenomenon by investigating the physiological consequences of spontaneous internal desynchronization and 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 SCN are 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 RGC peak around 474 nm. It is now believed that these RGCs provide the main light input to the circadian clock.
During the last year we have initiated a collaboration with Dr. Ian Fergusson (an expert in solid state lighting) at the Georgia Institute of Technology and 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 retinal ganglion cells. Indeed, our preliminary data indicate that these LEDs may be a valid countermeasure to prevent disfunctions of the circadian system that may occur in the space flight. In the next year of funding we plan to further investigate the use of these LEDs.
Research Impact/Earth Benefits:
Our project will provide important data on the cellular, molecular and 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.
Task Progress:
The experiments that we have carried out during the second year of funding have provided important new data about the functional organization of the mammalian circadian system. As proposed in the original application, we have terminated the experiment described in Specific Aims 1 (to investigate the physiological consequences of pineal Aa-nat mRNA desynchronization) and 2 (to investigate the cellular and molecular mechanisms responsible for the desynchronization between locomotor activity pattern and melatonin), and we have already published some of these new results. We have obtained the brains that are needed to perform the experiments that focus on the cellular and molecular mechanisms responsible for the desynchronization between locomotor activity pattern and melatonin.
Futhermore, we have developed a new series of blue narrow-band light-emitting diodes (LEDs) that are very effective in modulating some circadian parameters (melatonin suppression and phase-shift of the locomotor activity).
Bibliography Type:
Description: (Last Updated: 02/21/2008) Show Cumulative Bibliography Listing
Articles in Peer-reviewed Journals
Aguzzi J, Bullock NM, Tosini G. "Spontaneous internal desynchronization of locomotor activity and body temperature rhythms from plasma melatonin rhythm in rats exposed to constant dim light." J Circadian Rhythms. 2006 Apr 4;4:6. PMID: 16594995 , Apr-2006
Articles in Peer-reviewed Journals
Tosini G, Aguzzi J. "Effect of space flight on circadian rhythms." Adv Space Biol Med. 2005;10:165-74. Review. PMID: 16101107 , Oct-2005
Articles in Peer-reviewed Journals
Sakamoto K, Liu C, Kasamatsu M, Iuvone PM, Tosini G. "Intraocular injection of kainic acid does not abolish the circadian rhythm of arylalkylamine N-acetyltransferase mRNA in rat photoreceptors." Mol Vis. 2006 Feb 23;12:117-24. PMID: 16518309 , Feb-2006
Articles in Peer-reviewed Journals
Sakamoto K, Liu C, Kasamatsu M, Pozdeyev NV, Iuvone PM, Tosini G. "Dopamine regulates melanopsin mRNA expression in intrinsically photosensitive retinal ganglion cells."
Eur J Neurosci. 2005 Dec;22(12):3129-36. PMID: 16367779 , Dec-2005
Fiscal Year:
FY 2005
Task Last Updated:
11/01/2005
PI Name:
Tosini, Gianluca
Project Title:
Preventing Desynchronization of the Circadian System in Long-Term Space Flight
Division Name:
Human Research
Program/Discipline:
NSBRI Teams
Element/Subdiscipline:
Human Performance Factors, Sleep, and Chronobiology Team
Joint Agency Name:
Human Research Program Elements:
None
Human Research Program Risks::
None
Human Research Program Gaps:
None
PI Email:
tosinig@msm.edu
Fax:
404-752-1041
PI Organization Type:
UNIVERSITY
Phone:
404-756-5214
Organization Name:
Morehouse School of Medicine
PI Address 1:
720 Westview Dr. S.W.
PI Address 2:
PI Web Page:
http://www.msm.edu/neurohomepage/tosini.htm
City:
Atlanta
State:
GA
Zip Code:
30310-1495
Congressional District:
5
Comments:
Project Type:
GROUND
Solicitation:
2003 Biomedical Research & Countermeasures 03-OBPR-04
Start Date:
09/01/2004
End Date:
08/31/2007
No. of Post Docs:
0
No. of PhD Degrees:
0
No. of PhD Candidates:
0
No. of Master' Degrees:
0
No. of Master's Candidates:
0
No. of Bachelor's Degrees:
0
No. of Bachelor's Candidates:
0
Monitoring Center:
NSBRI
Contact Monitor:
Contact Phone:
Contact Email:
Flight Program:
Flight Assignment:
Key Personnel Changes/Previous PI:
COI Name (Institution):
Fukuhara, Chiaki (
Morehouse School of Medicine )
Grant/Contract No.:
NCC 9-58-HPF00407
Performance Goal No.:
Performance Goal Text:
Task Description:
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 the most important aspects of space flight is the absence of geophysical 24-h cycles, which, of course, affects the overall temporal organization of the organisms. In the case of long-duration manned space flight, 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 induce internal desynchronization in a 20-30 % of the rats tested. In the present research proposal we plan to further investigate this phenomenon, and to test specific countermeasures to obviate the occurrence of internal desynchronization in animals exposed to constant dim light. In particular, we will test if melatonin injection and exposure to brief pulse (skeleton photoperiod) of light (white light and light of different wavelength) can prevent internal desynchronization. Internal desynchronization has profound effects on the capability of the organisms to perform (mentally and physically) and to remain healthy. In this research proposal, we have designed a series of experiment aimed to understand the mechanisms that are responsible for the observed desynchronization and to test specific countermeasures aimed to prevent internal desynchronization. We believe that the model we have generated will be useful in to foreseeing and preventing dysfunction of the circadian system that may arise after long periods in the space environment where the normal cycle has been altered.
Research Impact/Earth Benefits:
Task Progress:
The experiments that we have carried out during this first year have provided important new data about the functional organization of the mammalian circadian system. As proposed in the original application, we have terminated the two experiments proposed in specific aim 1 (to investigate the physiological consequences of pineal Aa-nat mRNA desynchronization) and we have already collected the brains to perform the experiment proposed in Specific aim 2 (to investigate the cellular and molecular mechanisms responsible for the desynchronization between locomotor activity pattern and melatonin). As proposed in our research plan during the second year of funding, we will start the experiments described in Specific aim 3 (to investigate the use of melatonin and light (skeleton photoperiod) as effective countermeasures to prevent desynchronization).
Bibliography Type:
Description: (Last Updated: 02/21/2008) Show Cumulative Bibliography Listing
Articles in Peer-reviewed Journals
Fukuhara, C. Aguzzi, J. Bullock, N. Tosini, G. "Effect of Long-Term Exposure to Constant Dim Light on the Circadian System of Rats" N/A , Jan-2005
Presentation
Aguzzi, J. Bullock N., Tosini, G. "Preventing Desynchronization of the Circadian System" N/A
Jan-2005
Presentation
Bullock, N., Aguzzi, J., Tosini, G. "Long-term exposure to Constant Red Dim Light Desynchronizes the Circadian System of Rats" N/A
Jun-2005
Presentation
Tosini, G. "A Hierarchical Network of clocks regulates Circadian Rhythms in the Mammalian Retina" N/A
Jun-2005
Fiscal Year:
FY 2004
Task Last Updated:
03/31/2006
PI Name:
Tosini, Gianluca
Project Title:
Preventing Desynchronization of the Circadian System in Long-Term Space Flight
Division Name:
Human Research
Program/Discipline:
NSBRI Teams
Element/Subdiscipline:
Human Performance Factors, Sleep, and Chronobiology Team
Joint Agency Name:
Human Research Program Elements:
None
Human Research Program Risks::
None
Human Research Program Gaps:
None
PI Email:
tosinig@msm.edu
Fax:
404-752-1041
PI Organization Type:
UNIVERSITY
Phone:
404-756-5214
Organization Name:
Morehouse School of Medicine
PI Address 1:
720 Westview Dr. S.W.
PI Address 2:
PI Web Page:
http://www.msm.edu/neurohomepage/tosini.htm
City:
Atlanta
State:
GA
Zip Code:
30310-1495
Congressional District:
5
Comments:
Project Type:
GROUND
Solicitation:
2003 Biomedical Research & Countermeasures 03-OBPR-04
Start Date:
09/01/2004
End Date:
08/31/2007
No. of Post Docs:
No. of PhD Degrees:
No. of PhD Candidates:
No. of Master' Degrees:
No. of Master's Candidates:
No. of Bachelor's Degrees:
No. of Bachelor's Candidates:
Monitoring Center:
NSBRI
Contact Monitor:
Contact Phone:
Contact Email:
Flight Program:
Flight Assignment:
Key Personnel Changes/Previous PI:
COI Name (Institution):
Grant/Contract No.:
NCC 9-58-HPF00407
Performance Goal No.:
Performance Goal Text:
Task Description:
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 the most important aspects of space flight is the absence of geophysical 24-h cycles, which, of course, affects the overall temporal organization of the organisms. In the case of long-duration manned space flight, 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 induce internal desynchronization in a 20-30 % of the rats tested. In the present research proposal we plan to further investigate this phenomenon, and to test specific countermeasures to obviate the occurrence of internal desynchronization in animals exposed to constant dim light. In particular, we will test if melatonin injection and exposure to brief pulse (skeleton photoperiod) of light (white light and light of different wavelength) can prevent internal desynchronization. Internal desynchronization has profound effects on the capability of the organisms to perform (mentally and physically) and to remain healthy. In this research proposal, we have designed a series of experiment aimed to understand the mechanisms that are responsible for the observed desynchronization and to test specific countermeasures aimed to prevent internal desynchronization. We believe that the model we have generated will be useful in to foreseeing and preventing dysfunction of the circadian system that may arise after long periods in the space environment where the normal cycle has been altered.
Research Impact/Earth Benefits:
Task Progress:
New project for FY2004. No progress report this period.
Bibliography Type:
Description: (Last Updated: 02/21/2008) Show Cumulative Bibliography Listing
Bibliographic Listing of All Years
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