Simulated microgravity-induced oxidative stress in different areas of rat brain / 生理学报

Microgravity is known to produce a number of neurological disturbances during space flight; however, the underlying mechanism of these disturbances is yet to be elucidated. There have been some reports about the increased oxidative stress under microgravity or simulated microgravity. In the present study, we investigated the process of oxidative stress induced by simulated microgravity in different areas of rat brain, which may shed light on the mechanism of neurological disturbances and further neuroprotective research in spaceflight. After adaption for 7 d, 40 healthy male Sprague-Dawley rats were matched for body weight and randomly assigned to control groups (7, 14, 21 and 28 d) and tail-suspended simulated microgravity groups (7, 14, 21 and 28 d). The tail-suspended groups were treated with 30 angels of tail suspension and the control groups were treated similarly to the tail-suspended groups but without tail suspension. After the required times, different structures of rat brain, including cerebellum, cerebral cortex and hippocampus, were harvested and frozen for the further determination. Griess assay, thiobarbituric acid reactive substance (TBARS) assay, competitive ELISA and ferric reducing ability of plasma (FRAP) assay were used for the observation of the changes of reactive nitrogen species (RNS), malondialdehyde (MDA), nitrotyrosine (NT) and total antioxidant capacity (TAC), respectively. As shown in the results, there were different changes in various brain regions after tail suspension compared with control groups. (1) In cerebellum, NT increased after 7 d tail suspension, decreased after 14 d and increased again after 28 d; MDA increased after 14 d; RNS increased and TAC decreased after tail suspension for 21 d; (2) Increase of NT after14 d tail suspension, increase of MDA and decrease of TAC after 21 d were found in cerebral cortex; (3) In hippocampus, RNS increased after tail suspension for 7 d, decreased after 14 d and increased again after 28 d; MDA increased after 21 d; NT increased after 28 d; TAC increased after 7 d and recovered after 21 d. These results suggest that simulated microgravity induced by tail suspension increases the level of oxidative stress in rat brain; however, there are different features in different areas of rat brain. During the response to simulated microgravity, rat brain tissues present a similar process from adaptive response to irreversible oxidative damage.

Effects of parabolic flight on redox status in SH-SY5Y cells / 生理学报

Space flight is known to produce a number of neurological disturbances. The etiology is unknown, but it may involve increased oxidative stress. A line of experimental evidence indicates that space flight may disrupt antioxidant defense system and result in increased oxidative stress. In vitro studies found that abundant of NO was produced in rat pheochromocytoma (PC12) cells, SHSY5Y neuroblastoma cells, and protein nitration was increased in PC12 cells within a simulated microgravity rotating wall bioreactor high aspect ratio vessel system or clinostat system. In the present study, we observed the change of redox status in SH-SY5Y cells after parabolic flight, and studied the effects of key redox molecule, thioredoxin (TRX), during the altered gravity. SH-SY5Y cells were divided into four groups: control cells, control cells transfected with TRX, flight cells and flight cells transfected with TRX. The expression levels of 3-nitrotyrosine (3-NT), inducible nitric oxide synthase (iNOS), TRX and thioredoxin reductase (TRXR) were observed by immunocytochemical method. It was shown that after parabolic flight, the staining of 3-NT and TRX were enhanced, while the expression level of TRXR was down-regulated compared with control. As for flight cells transfected with TRX, the staining of 3-NT and iNOS were weakened compared with flight cells. These results obtained suggest that altered gravity may increase protein nitration, down-regulate TRXR and elicit oxidative stress in SH-SY5Y cells, while TRX transfection could partly protect cells against oxidative stress induced by parabolic flight.