Evaluation of Gene, Protein and Neurotrophin Expression in the Brain of Mice Exposed to Space Environment for 91 Days

Abstract

Effects of 3-month exposure to microgravity environment on the expression of genes and proteins in mouse brain were studied. Moreover, responses of neurobiological parameters, nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF), were also evaluated in the cerebellum, hippocampus, cortex, and adrenal glands. Spaceflight-related changes in gene and protein expression were observed. Biological processes of the up-regulated genes were related to the immune response, metabolic process, and/or inflammatory response. Changes of cellular components involving in microsome and vesicular fraction were also noted. Molecular function categories were related to various enzyme activities. The biological processes in the down-regulated genes were related to various metabolic and catabolic processes. Cellular components were related to cytoplasm and mitochondrion. The down-regulated molecular functions were related to catalytic and oxidoreductase activities. Up-regulation of 28 proteins was seen following spaceflight vs. those in ground control. These proteins were related to mitochondrial metabolism, synthesis and hydrolysis of ATP, calcium/calmodulin metabolism, nervous system, and transport of proteins and/or amino acids. Down-regulated proteins were related to mitochondrial metabolism. Expression of NGF in hippocampus, cortex, and adrenal gland of wild type animal tended to decrease following spaceflight. As for pleiotrophin transgenic mice, spaceflight-related reduction of NGF occured only in adrenal gland. Consistent trends between various portions of brain and adrenal gland were not observed in the responses of BDNF to spaceflight. Although exposure to real microgravity influenced the expression of a number of genes and proteins in the brain that have been shown to be involved in a wide spectrum of biological function, it is still unclear how the functional properties of brain were influenced by 3-month exposure to microgravity.

Morphological and Physiological Changes in Mature In Vitro Neuronal Networks towards Exposure to Short-, Middle- or Long-Term Simulated Microgravity

“…Recently, a payload for rodents, named Mice Drawer System (MDS) was built to house mice aboard the International Space Station (ISS) for investigating the long-term adaptation to space conditions [31]. It was reported that the expression of neuron growth factor (NGF) and brain-derived neurotrophic factor (BDNF) was reduced in brain regions such as the cortex and the hippocampus of spaceflown animals as compared to ground control ones [32]. The same study revealed that genes involved in long-term potentiation, axon guidance, neuronal growth, cone collapse, cell migration, dendrite branching and dendritic-spine morphology were up-regulated in the whole brain of mice exposed for 91 days to the ISS environment [32].…”

Are biological effects of space radiation really altered under the microgravity environment?

“…As previously described, gene expression is reported to be altered by the microgravity environment in space (Honda et al, 2012;Santucci et al, 2012;Blaber et al, 2013). Considering the alteration in gene expression associated with the chromatin conformation, further investigations are required to determine whether the chromatin structure is actually changed by microgravity.…”

“…Indeed, proteomics analysis is now frequently used in space studies including the ground-based study such as NASA human research program, radiobiology program, as described above. For example, gene expression is analysed in the recent space studies indicating its alteration by the microgravity environment in space (Honda et al, 2012;Santucci et al, 2012;Blaber et al, 2013). In these studies, such proteomics technologies were applied for studying lifespan control in C. elegans (Honda et al, 2012), evaluation of protein in the brain of mice (Santucci et al, 2012) and the mechanisms on bone loss in mice (Blaber et al, 2013).…”

“…For example, gene expression is analysed in the recent space studies indicating its alteration by the microgravity environment in space (Honda et al, 2012;Santucci et al, 2012;Blaber et al, 2013). In these studies, such proteomics technologies were applied for studying lifespan control in C. elegans (Honda et al, 2012), evaluation of protein in the brain of mice (Santucci et al, 2012) and the mechanisms on bone loss in mice (Blaber et al, 2013). Proteomic approach has also been proposed for studying age-dependent variations of cell response to low-dose IR exposure in rat astrocytes (Miura, 2009).…”

Ergonomic Challenges for Astronauts during Space Travel and the Need for Space Medicine

“…A number of studies in mice [30][31][32] suggest attenuation of neurotrophic factors associated with neurotransmission, it remains unclear how these changes may affect alteration in behavior and how such changes may translate into humans. It is essential to develop a deeper understanding on the potential for attenuation of brain function given the striking effect of spaceflight on structural plasticity and changes in grey matter volume [33], some of which may be attributable to fluid shifts.…”