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Jason Ciola
Pronouns
They/Them/Theirs
Job Title
Technical Research Assistant
Academic Rank
Department
Neurology
Authors
Jason C. Ciola†, Laura Wieg†, Fidelia Gaba, Brianna R. Colletti, Maren Schroeder, Robert G. Hinshaw, David M. Holtzman, Takashi Saito, Hiroki Sasaguri, Takaomi Saido, Cynthia A. Lemere
Principal Investigator
Cynthia Ann Lemere, PhD
Research Category: Neurosciences
Tags
Background: The CNS effects of GCRsim and gamma irradiation were investigated in female and male APPNL-F/NL-F knock-in (KI) mice bearing humanized APOE3 and APOE4 (APP;E3F and APP;E4F) to assess the risk of space-radiation on brain aging and Alzheimer’s disease.
Methods: 14 mo-old APP;E3F and APP;E4F mice underwent whole body irradiation with 0 Gy (sham), 0.75 Gy GCRsim, or 2 Gy Gamma at Brookhaven National Laboratory (BNL). Sham-irradiated 14 mo-old C57BL/6J mice acted as behavioral controls. To address effects of travel, 15 KI mice did not travel (NT) to BNL. Effects on locomotion, anxiety, motor skills and cognition were assessed at 20 mo followed by euthanasia and tissue harvest. S97 and Thioflavin S were used to quantify total and fibrillar amyloid-beta. Microhemorrhages were detected using a Prussian Blue stain.
Results: Male GCRsim-irradiated APP;E3F showed memory impairments. Unirradiated NT female and male APP;E3F mice performed better in tests of motor learning and short-term memory compared to unirradiated traveled sham controls. Males performed worse than females for anxiety and motor coordination. Regarding brain pathology, APP;E4F mice accumulated more amyloid-beta than their APP;E3F counterparts. A trend towards reduced amyloid-beta was seen in NT female APP;E3F compared to sham-irradiated KI mice.
Funding: NASA 80NSSC18K0810 (CAL)
This study aims to determine whether galactic cosmic radiation (GCR), which is found in outer space, might accelerate Alzheimer’s disease and brain aging in astronauts venturing to the moon and Mars. An amyloid-knockin Alzheimer’s-like mouse model was used, which harbors either gene variant, APOE4, associated with an increased risk of Alzheimer’s (APP;E4F) or a neutral variant, APOE3 (APP;E3F). Fourteen month-old mice underwent whole-body irradiation with 0 Gray (sham), 0.75 Gray GCRsim or 2 Gray gamma at Brookhaven National Laboratory (BNL). Unirradiated wildtype mice were included as controls for behavior. To look for travel effects, some mice did not travel to BNL. Effects on locomotion, anxiety, motor skills and cognition were assessed at 20 months of age followed by euthanasia and tissue harvest. Stains were used to detect amyloid-beta plaques, a hallmark of Alzheimer’s and microhemorrhages.
Male GCRsim-irradiated APP;E3F mice showed memory impairments. Unirradiated non-travel female and male APP;E3F mice performed better in tests of motor learning and short-term memory compared to unirradiated traveled mice. Males performed worse than their female counterparts for anxiety and motor coordination. APP;E4F mice accumulated more amyloid-beta than their APP;E3F counterparts, as expected, with fewer plaques seen in non-travel female APP;E3F mice.
Funding: NASA 80NSSC18K0810 (CAL)
