ACTIVATION OF NUCLEAR TRANSCRIPTION FACTOR–κB IN MOUSE BRAIN INDUCED BY a SIMULATED MICROGRAVITY ENVIRONMENT

Abstract

Microgravity induces inflammatory responses and modulates immune functions that may increase oxidative stress. Exposure to a microgravity environment induces adverse neurological effects; however, there is little research exploring the etiology of these effects resulting from exposure to such an environment. It is also known that spaceflight is associated with increase in oxidative stress; however, this phenomenon has not been reproduced in land-based simulated microgravity models. In this study, an attempt has been made to show the induction of reactive oxygen species (ROS) in mice brain, using ground-based microgravity simulator. Increased ROS was observed in brain stem and frontal cortex with concomitant decrease in glutathione, on exposing mice to simulated microgravity for 7 d. Oxidative stress-induced activation of nuclear factor-kappaB was observed in all the regions of the brain. Moreover, mitogen-activated protein kinase kinase was phosphorylated equally in all regions of the brain exposed to simulated microgravity. These results suggest that exposure of brain to simulated microgravity can induce expression of certain transcription factors, and these have been earlier argued to be oxidative stress dependent.

Proteomic Analysis of Mouse Hypothalamus under Simulated Microgravity

“…The control mice were maintained in normal cages with free access to drinking water and diet. To simulate microgravity, mice were suspended by their tail in the center of the cage but allowed to touch the floor with their front paws, and left for 7 days with free access to drinking water and food [9,10,13]. At the end of the experiment, the mice were euthanized by carbon dioxide asphyxiation.…”

“…At the end of the experiment, the mice were euthanized by carbon dioxide asphyxiation. Each brain was dissected out as described by our standardized procedures and, the hypothalamus was removed followed by snap frozen in liquid nitrogen [9,10]. The tissue was at −80°C for further experiments.…”

“…In addition oxidative stress has been argued as a potential cause of gene expression changes under microgravity. Oxidative stress induced NF κB in mouse brain has been reported in terrestrial model of microgravity [10]. The oxidative stress altered several signal transduction pathways and therefore was considered as one of the major factors that can modulate cellular signaling [12].…”

“…These changes included cytoskeleton proteins and proteins involved in metabolism. Induction of oxidative stress by microgravity has been detected both in simulated microgravity as well as in space [10,11]. In addition oxidative stress has been argued as a potential cause of gene expression changes under microgravity.…”

“…The oxidative stress altered several signal transduction pathways and therefore was considered as one of the major factors that can modulate cellular signaling [12]. We previously demonstrated generation of oxidative stress in different regions of mouse brain and the responses were discrete among different regions [10]. It therefore argues that increase in oxidative stress could elicit different changes specific to the different regions of the brain and thus induce confined proteome alterations.…”