Menu

 

The NASA Task Book
Advanced Search     
Back to Search Results    

Project Title:  Develop a Novel Single-Cell Biodosimetry for Brain Genomic Instability and Neurodegeneration to Predict Clinical Health Outcomes in Human Spaceflight Crews Reduce
Images: icon  Fiscal Year: FY 2024 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Animal Biology: Vertebrate  
 Start Date: 11/15/2020  
End Date: 11/30/2024  
Task Last Updated: 09/18/2023 		 Download report in PDF pdf
Principal Investigator/Affiliation:   Lu, Xiaohong  Ph.D. / LSU Health Shreveport 
Address:  1501 Kings Hwy 
BRI F5-22 
Shreveport , LA 71103 		 Email: xiaohong.lu@lsuhs.edu 
Phone: 3109803445  
Congressional District: 4 
Web:  
 Organization Type: UNIVERSITY 
Organization Name: LSU Health Shreveport 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Chancellor, Jeffery  Ph.D. Louisiana State University and A&M College 
Key Personnel Changes / Previous PI: Per the PI, the list of Co-Investigators has changed. During the past reporting period, the team has been working with the newly established bioinformatics center at Louisiana State University for the project, and Dr. Cvek was not involved. Dr. Harrison has moved to a new position and will no longer serve on this project. (Ed., 9/17/23)
Project Information: Grant/Contract No. 80NSSC21K0273 
Responsible Center: NASA ARC 
Grant Monitor: Griko, Yuri  
Center Contact: 650-604-0519 
Yuri.V.Griko@nasa.gov 
Unique ID: 14197  		Solicitation / Funding Source: 2018 Space Biology (ROSBio) NNH18ZTT001N-FG2. App D: Flight and Ground Space Biology Research 
Grant/Contract No.: 80NSSC21K0273 
Project Type: GROUND 
Flight Program:   		No. of Post Docs: 1 
No. of PhD Candidates: 1 
No. of Master's Candidates:  
No. of Bachelor's Candidates:   		No. of PhD Degrees:  
No. of Master's Degrees: 1 
No. of Bachelor's Degrees:  
Space Biology Element: (1) Animal Biology: Vertebrate
Space Biology Cross-Element Discipline: (1) Neurobiology
Space Biology Special Category: (1) Translational (Countermeasure) Potential
Flight Assignment/Project Notes: NOTE: End date changed to 11/30/2024 per NSSC information (Ed., 11/15/23)

NOTE: End date is 11/30/2023 (incorrectly listed in NSSC as 11/14/2021) per F. Hernandez/ARC (Ed., 7/27/21)

Task Description: As NASA plans future exploration missions to the Lunar and Martian surfaces, realistic ground-based analog studies and more predictive biodosimetry are needed to assess whether the space radiation poses a detrimental risk of brain genomic instability and neurodegeneration that leads to late-onset behavioral deterioration for spaceflight crews. Implementing a recently developed method of recreating the intravehicular (IVA) radiation environment expected on spaceflight vehicles and habitats and a novel genetic sensor, this proposal addresses Research Topic 3 – Animal Biology Studies in support of Human Space Exploration and Sub-topic AB1-A – Behavior and underlying neural function in Appendix D: Solicitation of Proposals for Flight and Ground Space Biology Research. We propose to determine how the space environment and sex affect brain genomic stability and consequent age-related brain structure and function changes. Our studies will support Human Space Exploration, by contributing the first biodosimetry for quantifying brain DNA instability and neurodegenerative changes to predict clinical health outcomes in human spaceflight crews and the utility of available ground-based analogs to realize basic mechanisms that can lead to the development of biologic counter-measures.

Research Impact/Earth Benefits: Our studies will support Human Space Exploration, by contributing the first biodosimetry for quantifying brain DNA instability and neurodegenerative changes to predict clinical health outcomes in human spaceflight crews and the utility of available ground-based analogs to realize basic mechanisms that can lead to the development of biologic counter-measures.

Task Progress & Bibliography Information FY2024 
Task Progress: 1. To evaluate the age and sex-dependent long-term consequences of galactic cosmic radiation (GCR) exposure on sensorimotor, cognition, and emotion, we have completed the longitudinal behavioral analysis in mice irradiated at NASA Space Radiation Laboratory (NSRL) in two groups. Group 1 mice (6 months of age) were irradiated with 80 cGy moderated iron (3.2 cGy/min, High dose rate, "HDR") (n = 22) or non-irradiated control (n = 16). 2. Group 2 mice (6 months of age) were irradiated with 30 or 75 cGy moderated iron (0.75 cGy/min, Low dose rate, "LDR”) (n = 12-17 per group), 30 or 75 cGy 5-ion simulated GCR (0.75 cGy/min “LDR”) (n = 16, 15 respectively), or non-irradiated control (n = 17). A wide variety of behavioral analyses were monitored in two time points at 2-4 months of and 10-14 months after irradiation. 3. Dosimetry analysis is ongoing at Louisiana State University-Baton Rouge (LSU-BR) with preliminary data. 4. Preliminary findings from the behavioral analysis results: Mice exposed to 75-80 cGy radiation show persistent deficits in sensorimotor function, including spontaneous activity, with stronger deficits in female mice. Irradiated mice show acute deficits in challenged movement (increased average time to cross balance beam), and age-dependent progressive development of accelerating rotarod deficits. Group 1 mice show acute hypersensitivity to stimuli (decreased time to remove facial adhesive). Cognitive function: Female mice develop working memory deficits. Differences in search strategies among irradiated and control mice during the probe day challenge of a spatial memory test may indicate cognitive differences associated with risk-taking behavior. Social and emotion: Exposed to modulated beam exposure impaired social interaction in mice. 5. We finished the analysis of sensor labeling in mice irradiated with moderated iron or simulated GCR (5-ion). A robust increase in Probe with a viRal proxy for the Instability of DNA surveillance/repair in Somatic brain Mosaicism (PRISM) labeling following simulated GCR exposure at three doses indicates an increase in radiation-induced genomic instability in CamkIIa-Cre-expressing cortical pyramidal neurons. Exposure to 80 cGy modulated Fe radiation at 3.2 cGy/min increases PRISM labeling in C57BL/6 mice. Exposure to 75 cGy GCR sim or modulated iron (0.75 cGy/min) increases PRISM labeling in Gt(Rosa) mice. 6. We have completed an RNA sequencing (RNAseq) study of mice irradiated with modulated iron. The pathway analysis is ongoing. 7. Brain mapping of the genomic instability in the brain after irradiation is ongoing. The work is ongoing to determine neuronal genomic instability in different brain regions and at 12 and 24 months after irradiation. 8. Single-cell pathology analysis in sensor-labeled neurons already identified highly intriguing cell senescence, neuroinflammation, and disruption of protein homeostasis, suggesting accelerated brain aging. More pathology analysis is ongoing.

Bibliography: Description: (Last Updated: 09/15/2022) 

Show Cumulative Bibliography
 
 None in FY 2024
Back to Search Results    
Project Title:  Develop a Novel Single-Cell Biodosimetry for Brain Genomic Instability and Neurodegeneration to Predict Clinical Health Outcomes in Human Spaceflight Crews Reduce
Images: icon  Fiscal Year: FY 2023 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Animal Biology: Vertebrate  
 Start Date: 11/15/2020  
End Date: 11/30/2023  
Task Last Updated: 09/15/2022 		 Download report in PDF pdf
Principal Investigator/Affiliation:   Lu, Xiaohong  Ph.D. / LSU Health Shreveport 
Address:  1501 Kings Hwy 
BRI F5-22 
Shreveport , LA 71103 		 Email: xiaohong.lu@lsuhs.edu 
Phone: 3109803445  
Congressional District: 4 
Web:  
 Organization Type: UNIVERSITY 
Organization Name: LSU Health Shreveport 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Cvek, Urska  Sc.D. Louisiana State University, Shreveport 
Chancellor, Jeffery  Ph.D. Louisiana State University and A&M College 
Harrison, Lynn  Ph.D. Louisiana State University 
Key Personnel Changes / Previous PI: n/a
Project Information: Grant/Contract No. 80NSSC21K0273 
Responsible Center: NASA ARC 
Grant Monitor: Griko, Yuri  
Center Contact: 650-604-0519 
Yuri.V.Griko@nasa.gov 
Unique ID: 14197  		Solicitation / Funding Source: 2018 Space Biology (ROSBio) NNH18ZTT001N-FG2. App D: Flight and Ground Space Biology Research 
Grant/Contract No.: 80NSSC21K0273 
Project Type: GROUND 
Flight Program:   		No. of Post Docs: 1 
No. of PhD Candidates: 1 
No. of Master's Candidates:  
No. of Bachelor's Candidates:   		No. of PhD Degrees:  
No. of Master's Degrees: 1 
No. of Bachelor's Degrees:  
Space Biology Element: (1) Animal Biology: Vertebrate
Space Biology Cross-Element Discipline: (1) Neurobiology
Space Biology Special Category: (1) Translational (Countermeasure) Potential
Flight Assignment/Project Notes: NOTE: End date is 11/30/2023 (incorrectly listed in NSSC as 11/14/2021) per F. Hernandez/ARC (Ed., 7/27/21)

Task Description: As NASA plans future exploration missions to the Lunar and Martian surfaces, realistic ground-based analog studies and more predictive biodosimetry are needed to assess whether the space radiation poses a detrimental risk of brain genomic instability and neurodegeneration that leads to late-onset behavioral deterioration for spaceflight crews. Implementing a recently developed method of recreating the intravehicular (IVA) radiation environment expected on spaceflight vehicles and habitats and a novel genetic sensor, this proposal addresses Research Topic 3 – Animal Biology Studies in support of Human Space Exploration and Sub-topic AB1-A – Behavior and underlying neural function in Appendix D: Solicitation of Proposals for Flight and Ground Space Biology Research. We propose to determine how the space environment and sex affect brain genomic stability and consequent age-related brain structure and function changes. Our studies will support Human Space Exploration, by contributing the first biodosimetry for quantifying brain DNA instability and neurodegenerative changes to predict clinical health outcomes in human spaceflight crews and the utility of available ground-based analogs to realize basic mechanisms that can lead to the development of biologic counter-measures.

Research Impact/Earth Benefits: Our studies will support Human Space Exploration, by contributing the first biodosimetry for quantifying brain DNA instability and neurodegenerative changes to predict clinical health outcomes in human spaceflight crews and the utility of available ground-based analogs to realize basic mechanisms that can lead to the development of biologic counter-measures.

Task Progress & Bibliography Information FY2023 
Task Progress: In the past year, we have two beamline exposures at the NASA Space Radiation Laboratory (NSRL). We used two method to develop a realistic ground-based simulation of galactic cosmic radiation (GCR) exposure. We also further modified a genetic sensor to generate a quantitative ratiometric sensor with membrane-tethered fluorescence protein to report different levels of genomic instability and visualize neuropathology. The radiometric sensors were administered in transgenic mice to label specific groups of neurons that are highly vulnerable to neurodegeneration. A radiation mimic, Bleomycin, increased genetic labeling neurons with genomic instability in the mouse brains. Simulated GCR exposure (iron modulator) at 80 cGy robustly increased the sensor labeling across the whole brain. The ratio of genetic labeling also increased, suggesting the sensor can report different levels of genomic instability. The DNA repair of the double stand breaks was also impaired. Mice that received simulated GCR exposure at 80 cGy showed multiple behavioral deficits (sensorimotor, cognition, and emotion/sociability) with gender differences three months post-irradiation. Finally, we also established the method to quantify single-neuron pathology and neuroinflammation and the method of mapping brain genotoxic stress using deep learning augmented volume imaging after GCR exposure.

Bibliography: Description: (Last Updated: 09/15/2022) 

Show Cumulative Bibliography
 
Articles in Peer-reviewed Journals El-Saadi MW, Tian X, Grames M, Ren M, Keys K, Li H, Knott E, Yin H, Huang S, Lu X-H. "Tracing brain genotoxic stress in Parkinson's disease with a novel single-cell genetic sensor. " Science Advances. 2022 Apr 15;8(15). http://dx.doi.org/10.1126/sciadv.abd1700 , Apr-2022
Back to Search Results    
Project Title:  Develop a Novel Single-Cell Biodosimetry for Brain Genomic Instability and Neurodegeneration to Predict Clinical Health Outcomes in Human Spaceflight Crews Reduce
Images: icon  Fiscal Year: FY 2022 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Animal Biology: Vertebrate  
 Start Date: 11/15/2020  
End Date: 11/30/2023  
Task Last Updated: 09/15/2021 		 Download report in PDF pdf
Principal Investigator/Affiliation:   Lu, Xiaohong  Ph.D. / LSU Health Shreveport 
Address:  1501 Kings Hwy 
BRI F5-22 
Shreveport , LA 71103 		 Email: xiaohong.lu@lsuhs.edu 
Phone: 3109803445  
Congressional District: 4 
Web:  
 Organization Type: UNIVERSITY 
Organization Name: LSU Health Shreveport 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Cvek, Urska  Sc.D. Louisiana State University, Shreveport 
Chancellor, Jeffery  Ph.D. Louisiana State University and A&M College 
Harrison, Lynn  Ph.D. Louisiana State University 
Key Personnel Changes / Previous PI: n/a
Project Information: Grant/Contract No. 80NSSC21K0273 
Responsible Center: NASA ARC 
Grant Monitor: Griko, Yuri  
Center Contact: 650-604-0519 
Yuri.V.Griko@nasa.gov 
Unique ID: 14197  		Solicitation / Funding Source: 2018 Space Biology (ROSBio) NNH18ZTT001N-FG2. App D: Flight and Ground Space Biology Research 
Grant/Contract No.: 80NSSC21K0273 
Project Type: GROUND 
Flight Program:   		No. of Post Docs: 1 
No. of PhD Candidates: 1 
No. of Master's Candidates:  
No. of Bachelor's Candidates:   		No. of PhD Degrees:  
No. of Master's Degrees: 1 
No. of Bachelor's Degrees:  
Space Biology Element: (1) Animal Biology: Vertebrate
Space Biology Cross-Element Discipline: (1) Neurobiology
Space Biology Special Category: (1) Translational (Countermeasure) Potential
Flight Assignment/Project Notes: NOTE: End date is 11/30/2023 (incorrectly listed in NSSC as 11/14/2021) per F. Hernandez/ARC (Ed., 7/27/21)

Task Description: As NASA plans future exploration missions to the Lunar and Martian surfaces, realistic ground-based analog studies and more predictive biodosimetry are needed to assess whether the space radiation poses a detrimental risk of brain genomic instability and neurodegeneration that leads to late-onset behavioral deterioration for spaceflight crews. Implementing a recently developed method of recreating the intravehicular (IVA) radiation environment expected on spaceflight vehicles and habitats and a novel genetic sensor, this proposal addresses Research Topic 3 – Animal Biology Studies in support of Human Space Exploration and Sub-topic AB1-A – Behavior and underlying neural function in Appendix D: Solicitation of Proposals for Flight and Ground Space Biology Research. We propose to determine how the space environment and sex affect brain genomic stability and consequent age-related brain structure and function changes. Our studies will support Human Space Exploration, by contributing the first biodosimetry for quantifying brain DNA instability and neurodegenerative changes to predict clinical health outcomes in human spaceflight crews and the utility of available ground-based analogs to realize basic mechanisms that can lead to the development of biologic counter-measures.

Research Impact/Earth Benefits: Our studies will support Human Space Exploration, by contributing the first biodosimetry for quantifying brain DNA instability and neurodegenerative changes to predict clinical health outcomes in human spaceflight crews and the utility of available ground-based analogs to realize basic mechanisms that can lead to the development of biologic counter-measures.

Task Progress & Bibliography Information FY2022 
Task Progress: • Constructed AAV-G22-Cre PRISM (adeno-associated viral) vectors and packaged in the neurotropic AAV-PhB.eB serotype with high titer and purity for non-invasive in vivo application (intravenous injection) in mice.

• We have determined the dose-response curve and the baseline dose of AAV-G22-Cre PRISM to report the spontaneous DNA damage response in the mouse brain. We tested the gene dosage dependency of the genetic sensor with G22 repeats. We examined 6 different doses (5x1011, 1x1011, 5x1010, 1x1010, 0.5x1010 VG/mouse) in vivo. We have determined the best titer/dosage of 1x1010 VG/mouse for in vivo application.

• We acquired Th-Cre, CamKII-Cre, D1-Cre, D2-Cre, Aai9 mouse breeding pairs from the Jackson Laboratory (JAX). We have been breeding these mice in C57BL/6J background. We already accumulated a sufficient number of mice for the simulated space radiation exposure at the NASA Space Radiation Laboratory (NSRL) this October 2021. • We successfully constructed the genetic sensor (biodosimetry) of neuronal genomic instability and validated the Cre dependency in vitro. These sensors will be used to determine space radiation-induced neuronal genomic instability in the most vulnerable neuronal cell types in multiple neurodegenerative disorders.

• We generated a quantitative ratiometric sensor: AAV-G34/G22/G13- mScarlet/fWasabi/fBFP PRISM vector and packaged it in AAV-PhB.eB serotype in high titer and purity for non-invasive in vivo application (intravenous injection) in mice.

• Intravenous systemic administration of AAV-G34/ G13- mScarlet/ fBFP PRISM sensor in different Cre driver lines (Drd1a. Drd2, TH Cre, CamkII Cre lines) was performed and we successfully labeled major neuronal cell types vulnerable to neurodegeneration, striatal medium spiny neurons, nigral dopamine neurons, hippocampal and cortical pyramidal neurons.

• Developed assays to quantify and confirm the mechanism of action of Dn to induce neuronal genomic instability using T7E1, Next Generation Sequencing (NGS), and capillary electrophoresis.

• We have made significant progress in optimizing the volume imaging of the iDISCO cleared mouse brains labeled with the genetic sensor of neuronal genomic instability.

• We have demonstrated that radiation mimic, Bleomycin, can increase AAV-G22-Cre dependent expression of AAV-G34/ G13- mScarlet/ fBFP PRISM sensor (systemic administration) genetic labelling in the mouse brains.

• We have scheduled and are ready for our first beamline exposures on 10/29-10/20/2021.

Bibliography: Description: (Last Updated: 09/15/2022) 

Show Cumulative Bibliography
 
Abstracts for Journals and Proceedings Knott EL, El-Saadi MW, Tian X, Chancellor J, Harrison L, Lu X-H. "A novel genetic biodosimetry of neuronal DNA damage response permits the risk assessment of space radiation-induced cognitive decline and neurodegeneration." Oral presentation at 37th Annual Meeting of the American Society for Gravitational and Space Research, Baltimore, MD, November 3-6, 2021.

Abstracts. 37th Annual Meeting of the American Society for Gravitational and Space Research, Baltimore, MD, November 3-6, 2021. , Nov-2021

Abstracts for Journals and Proceedings Knott EL, El-Saadi MW, Tian X, Chancellor J, Harrison L, Lu X-H. "A novel genetic biodosimetry of neuronal DNA damage response permits the risk assessment of space radiation-induced cognitive decline and neurodegeneration." Online and poster presentation at Neuroscience 2021 (Society for Neuroscience Annual Meeting), Virtual, November 8-11, 2021.

Abstracts. Neuroscience 2021 (Society for Neuroscience Annual Meeting), Virtual, November 8-11, 2021. , Nov-2021

Back to Search Results    
Project Title:  Develop a Novel Single-Cell Biodosimetry for Brain Genomic Instability and Neurodegeneration to Predict Clinical Health Outcomes in Human Spaceflight Crews Reduce
Images: icon  Fiscal Year: FY 2021 
Division: Space Biology 
Research Discipline/Element:
Space Biology: Animal Biology: Vertebrate  
 Start Date: 11/15/2020  
End Date: 11/30/2023  
Task Last Updated: 12/28/2020 		 Download report in PDF pdf
Principal Investigator/Affiliation:   Lu, Xiaohong  Ph.D. / LSU Health Shreveport 
Address:  1501 Kings Hwy 
BRI F5-22 
Shreveport , LA 71103 		 Email: xiaohong.lu@lsuhs.edu 
Phone: 3109803445  
Congressional District: 4 
Web:  
 Organization Type: UNIVERSITY 
Organization Name: LSU Health Shreveport 
Joint Agency:  
Comments:  
Co-Investigator(s)
Affiliation: 
Cvek, Urska  Sc.D. Louisiana State University, Shreveport 
Chancellor, Jeffery  Ph.D. Louisiana State University and A&M College 
Harrison, Lynn  Ph.D. Louisiana State University 
Project Information: Grant/Contract No. 80NSSC21K0273 
Responsible Center: NASA ARC 
Grant Monitor: Griko, Yuri  
Center Contact: 650-604-0519 
Yuri.V.Griko@nasa.gov 
Unique ID: 14197  		Solicitation / Funding Source: 2018 Space Biology (ROSBio) NNH18ZTT001N-FG2. App D: Flight and Ground Space Biology Research 
Grant/Contract No.: 80NSSC21K0273 
Project Type: GROUND 
Flight Program:   		No. of Post Docs:  
No. of PhD Candidates:  
No. of Master's Candidates:  
No. of Bachelor's Candidates:   		No. of PhD Degrees:  
No. of Master's Degrees:  
No. of Bachelor's Degrees:  
Space Biology Element: (1) Animal Biology: Vertebrate
Space Biology Cross-Element Discipline: (1) Neurobiology
Space Biology Special Category: (1) Translational (Countermeasure) Potential
Flight Assignment/Project Notes: NOTE: End date is 11/30/2023 (incorrectly listed in NSSC as 11/14/2021) per F. Hernandez/ARC (Ed., 7/27/21)

Task Description: As NASA plans future exploration missions to the Lunar and Martian surfaces, realistic ground-based analog studies and more predictive biodosimetry are needed to assess whether the space radiation poses a detrimental risk of brain genomic instability and neurodegeneration that leads to late-onset behavioral deterioration for spaceflight crews. Implementing a recently developed method of recreating the intravehicular (IVA) radiation environment expected on spaceflight vehicles and habitats and a novel genetic sensor, this proposal addresses Research Topic 3 – Animal Biology Studies in support of Human Space Exploration and Sub-topic AB1-A – Behavior and underlying neural function in Appendix D: Solicitation of Proposals for Flight and Ground Space Biology Research. We propose to determine how the space environment and sex affect brain genomic stability and consequent age-related brain structure and function changes. Our studies will support Human Space Exploration, by contributing the first biodosimetry for quantifying brain DNA instability and neurodegenerative changes to predict clinical health outcomes in human spaceflight crews and the utility of available ground-based analogs to realize basic mechanisms that can lead to the development of biologic counter-measures.

Research Impact/Earth Benefits:

Task Progress & Bibliography Information FY2021 
Task Progress: New project for FY2021.

Bibliography: Description: (Last Updated: 09/15/2022) 

Show Cumulative Bibliography
 
 None in FY 2021
Back to Search Results