Memory impairment, oxidative damage and apoptosis induced by space radiation: ameliorative potential of alpha-lipoic acid.
Exposure to high-energy particle radiation (HZE) may cause oxidative stress and cognitive impairment in the same manner that seen in aged mice. This phenomenon has raised the concerns about the safety of an extended manned mission into deep space where a significant portion of the radiation burden would come from HZE particle radiation. The present study aimed at investigating the role of alpha-lipoic acid against space radiation-induced oxidative stress and antioxidant status in cerebellum and its correlation with cognitive dysfunction. We observed spontaneous motor activities and spatial memory task of mice using pyroelectric infrared sensor and programmed video tracking system, respectively. Whole body irradiation of mice with high-LET (56)Fe beams (500 MeV/nucleon, 1.5 Gy) substantially impaired the reference memory at 30 day post-irradiation; however, no significant effect was observed on motor activities of mice. Acute intraperitoneal treatment of mice with alpha-lipoic acid prior to irradiation significantly attenuated such memory dysfunction. Radiation-induced apoptotic damage in cerebellum was examined using a neuronal-specific terminal deoxynucleotidyl transferase-mediated nick end-labeling method (NeuroTACS). Radiation-induced apoptotic and necrotic cell death of granule cells and Purkinje cells were inhibited significantly by alpha-lipoic acid pretreatment. Alpha-lipoic acid pretreatment exerted a very high magnitude of protection against radiation-induced augmentation of DNA damage (comet tail movement and serum 8-OHdG), lipid proxidation products (MDA+HAE) and protein carbonyls in mice cerebellum. Further, radiation-induced decline of non-protein sulfhydryl (NP-SH) contents of cerebellum and plasma ferric reducing power (FRAP) was also inhibited by alpha-lipoic acid pre-treatment. Results clearly indicate that alpha-lipoic acid is a potent neuroprotective antioxidant. Moreover, present finding also support the idea suggesting the cerebellar involvement in cognition.
Manda
Kailash
K
National Institute of Radiological Science, Chiba, Japan.
Ueno
Megumi
M
Anzai
Kazunori
K
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects; D002531:Cerebellum / Q000378:metabolism / Q000528:radiation effects*; D003359:Cosmic Radiation; D004249:DNA Damage / Q000502:physiology / Q000528:radiation effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood / Q000528:radiation effects; D015227:Lipid Peroxidation / Q000502:physiology / Q000528:radiation effects; D008297:Male; D018782:Maze Learning / Q000528:radiation effects*; D008568:Memory / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000528:radiation effects; D018696:Neuroprotective Agents / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology / Q000528:radiation effects; D050050:Protein Carbonylation / Q000502:physiology / Q000528:radiation effects; D011829:Radiation Dosage; D011837:Radiation-Protective Agents / Q000378:metabolism*; D011897:Random Allocation; D013026:Space Flight; D008063:Thioctic Acid / Q000378:metabolism*
D000975:Antioxidants; D018696:Neuroprotective Agents; D011837:Radiation-Protective Agents; D008063:Thioctic Acid; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine