In this issue
The Space Radiation Element is interested in promoting tissue sharing of samples that have already been irradiated, collected, and stored at our various PI's institutions. In the future, SR will consider encouraging tissue sharing of samples to be collected, with arrangements planned before scheduled runs. In July, we provided a questionnaire to collect your input and suggestions on the subject. Thank you to everyone who has provided their input, and we look forward to collecting the remaining questionnaires by mid-September.
New NASA Solicitations: NRA: NNJ13ZSA002N-RADIATION Ground-Based Studies in Space Radiobiology and NASA Specialized Centers of Research (NSCORs) for Ground-Based Studies inCancer Risks and Cognitive and Behavioral Central Nervous System Risks from Space Radiation
New NASA Solicitations: NRA: NNJ13ZSA002N-RADIATION Ground-Based Studies in Space Radiobiology andNASA Specialized Centers of Research (NSCORs) for Ground-Based Studies inCancer Risks and Cognitive and Behavioral Central Nervous System Risks from Space Radiation
The NASA Johnson Space Center has released NASA Research Announcement (NRA) NNJ13ZSA002N-RADIATION, entitled "Ground-Based Studies in Space Radiobiology." This NRA solicits ground-based proposals for the Space Radiation Program Element (SRPE) component of the Human Research Program (HRP). Proposals are solicited by the SRPE in the areas of CNS, cardiovascular, and cancer risks from space radiation and utilizing beams of high energy heavy ions simulating space radiation at the NASA Space Radiation Laboratory (NSRL), at Brookhaven National Laboratory in Upton, New York. This response area is Appendix E of the Human Exploration Research Opportunities (HERO) NRA (NNJ13ZSA002N).
The full text of the solicitation appendix is available on the NASA Research Opportunities homepage at http://tinyurl.com/2014-Radiation.
Step-1 proposals were due on June 27th while invited Step-2 proposals are due on September 9th. Final selections will be announced in December.
The HERO NRA including all open appendices is available through the NASA Research Opportunities homepage at:
NASA Selects 12 Space Radiobiology Research Proposals
NASA's Human Research Program will fund 12 ground-based research proposals using beams of high-energy, heavy ions to simulate space radiation to better understand the risks this radiation poses to humans.
The proposals were in response to the 2012 research announcement, "Ground-Based Studies in Space Radiobiology." The selected proposals are from 12 institutions in nine states, which will receive a total of about $15.6 million during a one- to four-year period.
These studies will help advance human exploration of space while limiting risks from space radiation. The research will employ new experimental approaches in understanding space radiation risks of cancer, heart and circulatory disease and long-term cognitive function. These studies will be conducted at the NASA Space Radiation Laboratory of the Brookhaven National Laboratory in Upton, N.Y.
The Human Research Program is managed by the Space Life and Physical Sciences Division in NASA's Human Exploration and Operations Mission Directorate.
The 25th Annual Space Radiation Investigator's Meeting, in conjunction with the 2014 NASA Human Research Program Investigators' Workshop, was held from Tuesday, February 11 through Thursday, February 13, 2014, at the Moody Gardens Hotel and Convention Center in Galveston, Texas.
Additional information and links to program schedule and abstracts are available on the Main Workshop Web Page.
Save the date for next year's Investigator's Workshop to be held the week of January 12, 2015 in Galveston, Texas.
Check the Space Radiation Integrative Risk Models Toolkit for some recently added tools including the new HemoDose, for rapid and accurate estimation of absorbed doses in adult radiation accident victims based on hematological parameters.
To guide medical personnel in making clinical decisions for effective medical management and treatment of exposed individuals in a radiology/nuclear disaster event, biomarkers that reflect radiation-induced biological changes have been employed to assess the extent of radiation injury. Among these, peripheral blood cell counts are traditionally regarded as the most practical and rapid diagnostic indicators. This is due to the fact that the hematopoietic system is the most vulnerable part of the human body to radiation damage, and the temporal changes of lymphocyte, granulocyte, and platelet concentration in peripheral blood after exposure are highly dose-dependent. Based upon years of physiological and pathophysiological investigation of mammalian hematopoietic systems, and rigorous coarse-grained bio-mathematical modeling and validation on species from rodent, to dog, non-human primate, and human, a new software tool HemoDose has been developed to use single or serial granulocyte, lymphocyte, leukocyte, or platelet counts after exposure to estimate the absorbed doses of adult victims very rapidly and accurately. Some patient data from historical accidents are utilized as examples to demonstrate the capabilities of these tools as a rapid point-of-care diagnostic or centralized high-throughput assay system in a large-scale radiological disaster scenario. Importantly, the HemoDose approach establishes robust correlations between the absorbed doses and a victim's blood cell counts not only in the early time window (1 or 2 days), but also in the very late phase (up to 4 weeks) after exposure. The Windows desktop version and the online web version can be accessed at /irModels/ for authorized users.
Health Standards for Long Duration and Exploration Spaceflight: Ethics Principles, Responsibilities, and Decision Framework
Released: April 2, 2014
REPORT AT A GLANCE
As the US space program evolves, propelled in part by increasing international and commercial collaborations, long duration or exploration spaceflights — such as extended stays on the International Space Station or missions to Mars — become more realistic. These types of missions will likely expose crews to levels of known risk that are beyond those allowed by current health standards, as well as to a range of risks that are poorly characterized, uncertain, and perhaps unforeseeable. As NASA and Congress discuss the next generation of NASA's missions and the US role in international space efforts, it is important to understand the ethical factors that drive decision making about health standards and mission design for NASA activities.
NASA asked the IOM to outline the ethics principles and practices that should guide the agency's decision making for future long duration or exploration missions that fail to meet existing health standards. The IOM's report identifies an ethics framework, which builds on the work of NASA and others, and presents a set of recommendations for ethically assessing and responding to the challenges associated with health standards for long duration and exploration spaceflight.
The Human Research Program Annual Report can be found at the following link: Full HRP Report.pdf
The 2014 NASA Space Radiation Summer School, which is held at the Brookhaven National Laboratory (BNL) on Long Island, New York has concluded. This year's session began on June 2nd and ran through June 20th. The goal of this course is to provide scientific and practical information to graduate students and scientists who are either new to the NASA program or to charged particle radiobiology. At the completion of the summer school, students received the full complement of training required to conduct their own experiments at BNL.
Course topics included DNA damage and repair, genotoxicity, cell cycle checkpoints, apoptosis, mutagenesis, genomic instability, epigenetics, cell and tissue signaling, neurodegeneration, systems biology, and the relationship of these processes to carcinogenesis and late degenerative effects following exposure to space radiation, as well as the space radiation environment, physics and biochemistry of charged particle interactions, track structure, dosimetry, accelerator operations, and space radiation protection.
Dr. John Norbury, from the NASA Langley Research Center was this year's Scientific Director. Look for the 2015 Summer School announcement next February.
The Software of the Year competition is a NASA-wide contest whose goal is to find the most outstanding software development efforts across the Agency on an annual basis. Our HRP SRPE team won the Runner up position for producing the 2012 NASA Space Cancer Risk Model. This is a notable accomplishment that recognizes the substantial expertise and effort of the SRPE scientists. In addition, the team members were awarded The Space Act Award for the NASA Space Cancer Risk (NSCR) 2012 Version 1.0 Web Server by the NASA Inventions and Contributions Board. The ICB, established by the Space Act of 1958, is responsible for the Space Act Awards whose purpose is to reward and promote outstanding scientific or technical contributions sponsored, adopted, supported or used by NASA that are significant to aeronautics and space activities. Therefore, we congratulate these team members, including USRA employees Lori Chappell, Myung-Hee Kim, Shaowen Hu, Hatem Nounu, Ianik Plante, and NASA employees Pat O'Neill and retired Scientist Francis Cucinotta.
On Thursday, Jan. 30, at JSC, the Technology Transfer Office within the Strategic Opportunity and Development Office hosted the Invention and Contributions Board (ICB) Awards and the JSC Exceptional Software Awards ceremony.
Pictured from the left are: Tondra Allen, Assistant Chair for the SOY Committee Board, Pat O'Neill, Shaowen Hu, Myung-Hee Kim, Ianik Plante, Laurie Chappell, Hatem Nounu, Dr. Ellen Ochoa, Director of JSC.
Amelia Eisch, Ph.D.
Overview of Research Interests
Inability of the brain to appropriately "adapt" to environmental or physiological changes may contribute to — or exacerbate — brain dysfunction, and even contribute to the development or prolongation of psychiatric disorders like addiction, depression or post-traumatic stress disorder. My laboratory studies numerous mediators of neuroplasticity, including a relatively novel one: the generation of new neurons in the adult brain, or “adult neurogenesis”. One way of thinking about this aspect of my laboratory’s research is that we aim to understand "what is adult neurogenesis good for?" as well as "what is good for adult neurogenesis?" My work shows that adult neurogenesis is important in many motivated behaviors that have relevance not only for general learning and memory but also for animal models of addiction, depression, and post-traumatic stress disorder. As adult neurogenesis is profoundly influenced by space radiation, and as space radiation and the space flight experience are robust environmental and physiological stimuli, we are currently very interested in understanding how space radiation and the space flight experience influences adult neurogenesis and, in particular, how it influences motivated behaviors that are critical for successful completion of the mission. For more on my laboratory's research, please visit the Eisch Lab Website.
Select Honors and Awards
Functional and mechanistic exploration of an adult neurogenesis-promoting small molecule. Petrik D, Jiang Y, Birnbaum SG, Powell CM, Kim MS, Hsieh J, Eisch AJ FASEB J. 2012 Aug 26 8 3148-62.
The neurogenesis hypothesis of affective and anxiety disorders: are we mistaking the scaffolding for the building? Petrik D, Lagace DC, Eisch AJ Neuropharmacology 2012 Jan 62 1 21-34.
Not(ch) just development: Notch signaling in the adult brain. Ables JL, Breunig JJ, Eisch AJ, Rakic P Nat. Rev. Neurosci. 2011 May 12 5 269-83.
Notch1 is required for maintenance of the reservoir of adult hippocampal stem cells. Ables JL, Decarolis NA, Johnson MA, Rivera PD, Gao Z, Cooper DC, Radtke F, Hsieh J, Eisch AJ J. Neurosci. 2010 Aug 30 31 10484-92.
Withdrawal from cocaine self-administration enhances hippocampal neurogenesis, but normalizes proliferation and maturation of neural progenitors, in the adult dentate gyrus subgranular zone. Noonan MA, Choi K-H, Self DW, Eisch AJ. The Journal of Neuroscience 2008 28 2516-26.
Dynamic contribution of nestin-expressing stem cells to adult neurogenesis. Lagace DC, Whitman MC, Noonan MA, Ables JL, DeCarolis NA, Arguello AA, Donovan MH, Fischer SJ, Farnbauch LA, Beech RD, Dileone RJ, Greer CA, Mandyam CD, Eisch AJ. The Journal of Neuroscience. 2007 27 12623-12629.
Opiates inhibit neurogenesis in the adult rodent dentate gyrus. Eisch AJ, Barrot M, Schad CA, Self DW, Nestler EJ. Proceedings of the National Academy of Sciences, USA 2000 97 7579-7584.\
Lagace DC, Donovan MH, Farnbauch LA, DeCarolis NA, Berton O, Nestler EJ, Krishnan V, Eisch AJ. Adult hippocampal neurogenesis is functionally important for stress-induced social avoidance. Proceedings of the National Academy of Sciences, USA. 107(9):4436-41 (2010). PMID 20176946, PMC 2840117.
Johnson MA, Ables JL, Eisch AJ. Cell-intrinsic signals that regulate adult neurogenesis in vivo: insights from inducible approaches. BMB Reports. 42(5): 245-259 (2009). PMID 19470237, PMC3601036.
Noonan MA, Bulin SA, Fuller D, Eisch AJ. Reduction of adult hippocampal neurogenesis confers vulnerability in an animal model of addiction. The Journal of Neuroscience, 30(1):304-315 (2010). PMID 20053911, PMC 2844797.
Ables JL, DeCarolis NA, Johnson MA, Rivera PD, Gao Z, Cooper DC, Radtke F, Hsieh J, Eisch AJ. Notch1 is required for maintenance of the reservoir of adult hippocampal stem cells. The Journal of Neuroscience, 30(31):10484-92 (2010).PMID 20685991, PMC 2935844. Recommended article, Faculty of 1000 Biology
Rivera PD*, Shih H-Y*, LeBlanc JA, Cole MG, Amaral WZ, Mukherjee S, Zhang S, Lucero MJ, DeCarolis NA, Chen BPC, Eisch AJ. Acute and Fractionated Exposure to High-LET 56Fe HZE Particle Radiation Both Result in Similar Long-Term Deficits in Adult Hippocampal Neurogenesis. Radiation Research. (Epub Dec 9 2013) Dec;180(6):658-67. doi: 10.1667/RR13480.1. (2013) PMID 24320054, PMC 3930069. *authors contributed equally to this work.
Latchney SE, Rivera PD, Mao XW, Ferguson VL, Bateman TA, Stodieck LS, Nelson GA, Eisch AJ. The effect of spaceflight on mouse olfactory bulb volume, neurogenesis, and cell death indicates the protective effect of novel environment. Journal of Applied Physiology. In press.
Showed that (in addition to opiates) cocaine also alters adult hippocampal neurogenesis (see Noonan et al., 2008). This suggests that preventing or reversing the drug abuse-induced decrease in hippocampal neurogenesis may be a novel treatment for addiction.
Elucidated the surprising reverse relationship: decreased adult hippocampal neurogenesis is a risk factor in animal models of addiction (see Noonan et al., 2010). This work suggested that stimuli that may decrease neurogenesis - like early life stress - may actually be causal in driving addiction later in life.
Discovered another surprising role for new neurons in the hippocampus: mediating coping response to a socially-stressful experience (see Lagace et al., 2010). Using a rodent model of post-traumatic stress disorder, this work suggested that the number of new neurons may indeed encode the “memory” of a stressful event. This ran counter to work showing that “stress decreases neurogenesis”, but was the first work to examine the functional role of decreased hippocampal neurogenesis in an ethologically-relevant social stress model, and thus highlighted that addition of new neurons may indeed be related to better memory, even if the memory is of a stressful event.
Identified an in vivo neurogenic and memory-improving function for a novel small molecule, and defined a molecular target for the neurogenic enhancement (see Petrik et al., 2012). This work now allows application of this neurogenic small molecule to other questions: will enhancement of adult neurogenesis help break the cycle of psychiatric disorders such as addiction, depression, or anxiety?
Discovered the heterogeneity of neural stem cells in the adult mouse hippocampus (see DeCarolis et al., 2013). In addition to helping reconcile the results from different transgenic mouse lines used to study adult neurogenesis, this work emphasized that the heterogeneity of radial glial cells seen during development may indeed be of functional importance in the adult as well.
Worked with NASA colleagues to assess the impact of acute vs. fractionated ground based space radiation on adult neurogenesis and behavior (Rivera, Shih, et al., 2013), as well as the impact of space flight experience on the generation of neurons in another brain region, the olfactory bulb (Latchney et al., in press). Actively exploring the influence of space radiation on “mission critical” brain functions in laboratory animals, including stress- and anxiety-based as well as executive function measures.
Questions and Answers
I was always interested in the connection between brain and behavior, but until late in college I focused on the “behavior” side with my major in Psychology with a Biology emphasis. However, there were several courses I took late in college that spurred my greater interest in the neural underpinnings of behavior. The most riveting for me was a small college seminar on “Biological Basis of Drugs of Abuse” which opened the world of neuroscience to me, and led me to take Neurobiology and the associated lab during my senior year. I was inspired by these courses to envision a career where I could understand the neurobiology of both normal and pathologically motivated behavior. I had briefly considered pursuing medicine or clinical research, but when I was in graduate school (in the 1990s) there was a groundswell of literature — performed by researchers like George Koob at Scripps, Eric Nestler and Ron Duman at Yale among many others — showing the power that basic neuroscience had in dissecting the neural underpinning of behavior. I wanted to be part of that. In addition, my parents are both academics (my mother was a geriatric nurse practitioner and did some research, while my father is a distinguished professor of Organic Chemistry), and the freedom to ask and answer questions via research was very appealing to me.
My laboratory’s NASA work has focused on two aspects so far: the impact of space radiation on stem cells and the generation of new neurons in the hippocampus, an area of the adult brain that contributes to memory and mood regulation, and the impact of the space flight experience on new neurons in the olfactory bulb.
The work on space radiation and stem cells has been done in collaboration with Benjamin P.C. Chen, my colleague at UT Southwestern Medical Center, and was published in 2013 in Radiation Research. For this study, Phil Rivera in my lab and Eric Shih in the Chen lab led the team to find that acute and fractionated space radiation had similarly negative effects on the generation of new neurons in the adult mouse hippocampus, but did not change the number of stem cells in the hippocampus. There were three main implications of this work. First, the “decreased adult hippocampal neurogenesis” we report after both acute and fractionated exposure may contribute to the cognitive deficits seen in other published studies. Second, the lack of influence on the number of hippocampal stem cells suggests regenerative potential exists in the hippocampus of these mice. Finally, these data suggest that the way space radiation is mimicked on Earth — typically via one acute exposure to mimic a multi-year space flight — is similar to a fractionated exposure. We are currently following up this work to see what the functional/behavioral effects are of exposure to space radiation. In fact, the influence of space radiation on “mission critical” behaviors and brain functions — including memory, mood, anxiety, and response to stress — is a central theme of our future NASA work.
The work on the impact of the space flight experience on new neurons in the olfactory bulb was just accepted into the Journal of Applied Physiology, and was been done in collaboration with many scientists, including Greg Nelson and Vivian Mao of Loma Linda, Virgina Ferguson of U Colorado Boulder, Louis Stodieck of BioServ in Boulder, CO, and Ted Bateman of U North Carolina, and my lab members, led by my postdoctoral fellow, Sarah Latchney. I emphasize the team nature of this project because it was truly a team effort in arranging the tissue collection from mice sent on the last space shuttle mission (STS-135), processing the tissue, and examining the generation of new neurons in the olfactory bulb of the mice sent into space, compared to controls housed on Earth. The main finding of this work was that mice housed in Animal Enclosure Modules (AEMs) on Earth had more olfactory bulb neurogenesis and larger bulbs than those in standard housing on Earth and in most cases than those in AEMs and sent on STS-135. This central finding emphasizes the importance of a novel environment in driving brain plasticity, and the importance of including correct control conditions in space flight studies. For example, if we had not had samples from mice housed in standard housing on Earth we might have concluded that space flight diminishes olfactory bulb size and neurogenesis. However, inclusion of this important control allowed us to conclude that space flight actually brought the olfactory bulb size and number of new neurons back within the range of the standard housing control mice on Earth. We hope to be able to work with more brain tissue from animals sent into space in the future, and would particularly be interested to see the functional influence of space flight, for example, on olfactory discrimination and even hippocampal functions like memory and mood.
It is very important to me that I have provided the field of neurogenesis and adult neural stem cells with a novel transgenic mouse — the nestinCreERT2 transgenic mouse — that enables tracking and inducibly genetic deletion in neural stem cells and their progeny. This tool, which has been received by over 100 laboratories all over the world, makes it possible to do more in-depth research into the nature of adult neural stem cells, including in vivo imaging and assessment of their function. It is also very important to me to have funding from a variety of sources, including NASA but also NIH and smaller but pivotal organizations like the Brain and Behavior Foundation. The diversity of research these funds have provided me in the past and present allows my laboratory to pursue our overarching theme: what are the neural underpinnings of motivated behavior, both ‘normal’ — like seeking a food treat at the end of a maze — and pathological — like compulsive seeking of a drug of abuse, or excessive anxiety behavior? I am really intrigued to see how these brain functions will be altered by both space flight and space radiation exposure. My involvement with NASA colleagues and attendance at the HRP Workshops and other meetings really provides me with the ‘big picture’ (from cells up to humans) that I think is missing from many other branches of science. A final accomplishment that is important to me is the fact I have trained almost 100 people in my laboratory, from high school students up to postdoctoral fellows. I am determined to pass on best practices in neuroscience to everyone in my laboratory, as it is very important to me to participate as much as I can in training the next generation of neuroscientists.
The following text is an English translation of a document from the Institute of Biomedical Problems, Moscow.
The staff of the Institute has suffered a great loss — Vladislav M. Petrov , Chief of the radiation safety of manned space flights, died at age seventy six. With a long tenure at the Institute (since 1964), Vladislav M. has gone from a research assistant to the Head of Department. During this period, he carried out a large amount of scientific and scientific-organization activities. Under his leadership, a new set of standard radiation monitoring equipment was developed, as were the scientific and methodological bases for radiation safety of current and future manned space flights. For his scientific and production activities, VM Petrov was frequently thanked by the Institute (IBMP) , 3rd Main Office, and the Ministry of Health of the USSR. He was awarded the Order "Badge of Honor ", the "Veteran of Labor" Medal " 850th Anniversary of Moscow " , the commemorative medal of the YA Gagarin" for "Service to the Motherland" II Art., medal of honor named after the first Cosmonaut ,Yuri Gagarin, and was a laureate of the State Prize of the USSR. (We have) lost a great scientist and a true patriot of Russian science who remained in service until his last day. His work plans were not realized of flying man outside the magnetosphere of the Earth, to the Moon and Mars... The bright memory of Vladislav Mikhailovich Petrov - scientist and man - remains with us forever.
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