TY - JOUR
T1 - Targeting hippocampal neurogenesis to protect astronauts’ cognition and mood from decline due to space radiation effects
AU - McNerlin, Clare
AU - Guan, Fada
AU - Bronk, Lawrence
AU - Lei, Kevin
AU - Grosshans, David
AU - Young, Damian W.
AU - Gaber, M. Waleed
AU - Maletic-Savatic, Mirjana
N1 - Funding Information:
This work was supported by the Translational Research Institute for Space Health through NASA Cooperative Agreement NNX16AO69A, grant RAD01013 (M.M.S).
Publisher Copyright:
© 2022
PY - 2022/11
Y1 - 2022/11
N2 - Neurogenesis is an essential, lifelong process during which neural stem cells generate new neurons within the hippocampus, a center for learning, memory, and mood control. Neural stem cells are vulnerable to environmental insults spanning from chronic stress to radiation. These insults reduce their numbers and diminish neurogenesis, leading to memory decline, anxiety, and depression. Preserving neural stem cells could thus help prevent these neurogenesis-associated pathologies, an outcome particularly important for long-term space missions where environmental exposure to radiation is significantly higher than on Earth. Multiple developments, from mechanistic discoveries of radiation injury on hippocampal neurogenesis to new platforms for the development of selective, specific, effective, and safe small molecules as neurogenesis-protective agents hold great promise to minimize radiation damage on neurogenesis. In this review, we summarize the effects of space-like radiation on hippocampal neurogenesis. We then focus on current advances in drug discovery and development and discuss the nuclear receptor TLX/NR2E1 (oleic acid receptor) as an example of a neurogenic target that might rescue neurogenesis following radiation.
AB - Neurogenesis is an essential, lifelong process during which neural stem cells generate new neurons within the hippocampus, a center for learning, memory, and mood control. Neural stem cells are vulnerable to environmental insults spanning from chronic stress to radiation. These insults reduce their numbers and diminish neurogenesis, leading to memory decline, anxiety, and depression. Preserving neural stem cells could thus help prevent these neurogenesis-associated pathologies, an outcome particularly important for long-term space missions where environmental exposure to radiation is significantly higher than on Earth. Multiple developments, from mechanistic discoveries of radiation injury on hippocampal neurogenesis to new platforms for the development of selective, specific, effective, and safe small molecules as neurogenesis-protective agents hold great promise to minimize radiation damage on neurogenesis. In this review, we summarize the effects of space-like radiation on hippocampal neurogenesis. We then focus on current advances in drug discovery and development and discuss the nuclear receptor TLX/NR2E1 (oleic acid receptor) as an example of a neurogenic target that might rescue neurogenesis following radiation.
KW - Drug discovery
KW - Hippocampus
KW - Neurogenesis
KW - Space radiation
KW - TLX/NR2E1 (oleic acid receptor)
UR - http://www.scopus.com/inward/record.url?scp=85136642162&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85136642162&partnerID=8YFLogxK
U2 - 10.1016/j.lssr.2022.07.007
DO - 10.1016/j.lssr.2022.07.007
M3 - Article
C2 - 36336363
AN - SCOPUS:85136642162
SN - 2214-5524
VL - 35
SP - 170
EP - 179
JO - Life Sciences in Space Research
JF - Life Sciences in Space Research
ER -