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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 occurred 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.

SUBMITTER: Santucci D

PROVIDER: S-EPMC3392276 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Evaluation of gene, protein and neurotrophin expression in the brain of mice exposed to space environment for 91 days.

Santucci Daniela D Kawano Fuminori F Ohira Takashi T Terada Masahiro M Nakai Naoya N Francia Nadia N Alleva Enrico E Aloe Luigi L Ochiai Toshimasa T Cancedda Ranieri R Goto Katsumasa K Ohira Yoshinobu Y

PloS one 20120709 7

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 proc ...[more]

PMID: 22808101

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Project description:Cocaine use during adolescence decreases the likelihood that individuals will seek treatment for recurrent drug use. In rodents, developmental cocaine exposure weakens action-consequence decision-making, causing a deferral to familiar, habit-like behavioral response strategies. Here, we aimed to improve action-outcome decision-making. We found that acute pharmacological stimulation of the tyrosine/tropomyosin receptor kinase B (trkB) via 7,8-dihydroxyflavone (7,8-DHF) or 3,4-methylenedioxymethamphetamine (MDMA) blocked cocaine-induced habit biases by strengthening memory for action-outcome associations. We believe that MDMA acts by stimulating neurotrophin/trkB systems in the orbitofrontal cortex (OFC), a region involved in prospectively evaluating the consequences of one's action, because 1) MDMA also increased brain-derived neurotrophic factor (BDNF) in the OFC, 2) MDMA corrected habit biases due to Bdnf loss in the OFC, and 3) overexpression of a truncated isoform of trkB occluded the memory-enhancing effects of MDMA. Thus, selecting actions based on their consequences requires BDNF-trkB in the OFC, the stimulation of which may improve goal attainment in both drug-naïve and cocaine-exposed individuals. SIGNIFICANCE STATEMENT: Cocaine use during adolescence decreases the likelihood that individuals will seek treatment for recurrent drug use, even as adults. Understanding how early-life cocaine exposure impacts goal-oriented action and prospective decision-making in adulthood is thus important. One key aspect of goal-directed decision-making is anticipating the consequences of one's actions, a process that likely involves the orbitofrontal cortex (OFC). In rodents, developmental cocaine exposure weakens action-consequence decision-making, causing a deferral to familiar, habit-like behavioral response strategies. Here, we report that we can improve memory for action-consequence relationships by stimulating neurotrophic factors, which support cell survival, development, and plasticity in the brain. With strengthened action-consequence associations, cocaine-exposed mice regain the ability to optimally select actions based on their likely outcomes. Brain region-selective manipulations reveal that neurotrophin systems in the OFC are necessary for stable memory of action-consequence relationships.

Dataset Information

Evaluation of gene, protein and neurotrophin expression in the brain of mice exposed to space environment for 91 days.

Publications

Evaluation of gene, protein and neurotrophin expression in the brain of mice exposed to space environment for 91 days.

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