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

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.

[1]  T. Yasuhara,et al.  Lack of exercise, via hindlimb suspension, impedes endogenous neurogenesis , 2007, Neuroscience.

[2]  S. Barnes,et al.  Proteomic analysis of mice hippocampus in simulated microgravity environment. , 2006, Journal of proteome research.

[3]  A. Privat,et al.  Influence of hypergravity on the development of monoaminergic systems in the rat spinal cord. , 1998, Brain research. Developmental brain research.

[4]  C. Däpp,et al.  During Atrophy and Recovery of Mouse Soleus Muscle Transcriptional Reprogramming and Ultrastructure Transcriptional Reprogramming and Ultrastructure during Atrophy and Recovery of Mouse Soleus Muscle , 2004 .

[5]  G. Weskamp,et al.  An Enzyme‐Linked Immunoassay for Nerve Growth Factor (NGF): A Tool for Studying Regulatory Mechanisms Involved in NGF Production in Brain and in Peripheral Tissues , 1987, Journal of neurochemistry.

[6]  E. Alleva,et al.  Neurobehavioural effects of hypergravity conditions in the adult mouse , 2000, Neuroreport.

[7]  A. Musarò,et al.  Adaptation of Mouse Skeletal Muscle to Long-Term Microgravity in the MDS Mission , 2012, PloS one.

[8]  Y. Ohira,et al.  Role(s) of gravitational loading during developing period on the growth of rat soleus muscle fibers. , 2010, Journal of applied physiology.

[9]  C. Hall,et al.  p80 ROKα binding protein is a novel splice variant of CRMP‐1 which associates with CRMP‐2 and modulates RhoA‐induced neuronal morphology , 2002, FEBS letters.

[10]  Stephen C. Harris,et al.  Rat toxicogenomic study reveals analytical consistency across microarray platforms , 2006, Nature Biotechnology.

[11]  G. Adler,et al.  Neurotrophin and GDNF expression increases in rat adrenal glands during experimental colitis. , 2001, Neuro endocrinology letters.

[12]  E. Alleva,et al.  Stress and nerve growth factor Findings in animal models and humans , 2002, Pharmacology Biochemistry and Behavior.

[13]  D. W. Wu,et al.  [Effects of tail suspension on learning and memory function of mice]. , 2000, Hang tian yi xue yu yi xue gong cheng = Space medicine & medical engineering.

[14]  I. Nonaka,et al.  Tension- and afferent input-associated responses of neuromuscular system of rats to hindlimb unloading and/or tenotomy. , 2004, American journal of physiology. Regulatory, integrative and comparative physiology.

[15]  Effects of acute and repeated daily exposure to hypergravity on spatial learning in mice , 2003, Neuroscience Letters.

[16]  A. Oliverio,et al.  Hippocampal gene expression is modulated by hypergravity , 2004, The European journal of neuroscience.

[17]  E R Kandel,et al.  A selective role of calcineurin aalpha in synaptic depotentiation in hippocampus. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[18]  E. Alleva,et al.  Effect of hypergravity on the mouse basal expression of NGF and BDNF in the retina, visual cortex and geniculate nucleus: correlative aspects with NPY immunoreactivity , 2001, Neuroscience Letters.

[19]  B. McEwen Stress and hippocampal plasticity. , 1999, Annual review of neuroscience.

[20]  A. Cellerino,et al.  Brain-Derived Neurotrophic Factor Modulates the Development of the Dopaminergic Network in the Rodent Retina , 1998, The Journal of Neuroscience.

[21]  D. Spray,et al.  Effect of microgravity on gene expression in mouse brain , 2008, Experimental Brain Research.

[22]  M. Baxter,et al.  Purkinje cell loss accompanies motor impairment in rats developing at altered gravity , 2005, Neuroreport.

[23]  J. Shih,et al.  Mice Deficient in Collapsin Response Mediator Protein-1 Exhibit Impaired Long-Term Potentiation and Impaired Spatial Learning and Memory , 2007, The Journal of Neuroscience.

[24]  J. Schittny,et al.  Mechano-regulated Tenascin-C orchestrates muscle repair , 2008, Proceedings of the National Academy of Sciences.

[25]  K. Akassoglou,et al.  Learning abilities, NGF and BDNF brain levels in two lines of TNF-α transgenic mice, one characterized by neurological disorders, the other phenotypically normal , 1999, Brain Research.

[26]  R. Tibshirani,et al.  Significance analysis of microarrays applied to the ionizing radiation response , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[27]  I. Nonaka,et al.  Regulation of the properties of rat hind limb muscles following gravitational unloading. , 2002, The Japanese journal of physiology.

[28]  Stephen Barnes,et al.  Proteomic Analysis of Mouse Hypothalamus under Simulated Microgravity , 2008, Neurochemical Research.

[29]  T. Mukai,et al.  Bone mass loss due to estrogen deficiency is compensated in transgenic mice overexpressing human osteoblast stimulating factor-1. , 1997, Biochemical and biophysical research communications.

[30]  V. Edgerton,et al.  Effects of 14 days of spaceflight and nine days of recovery on cell body size and succinate dehydrogenase activity of rat dorsal root ganglion neurons , 1997, Neuroscience.

[31]  I. Nonaka,et al.  Afferent input-associated reduction of muscle activity in microgravity environment , 2002, Neuroscience.

[32]  U. Otten,et al.  Increased levels of NGF in sera of systemic lupus erythematosus patients. , 1993, Neuroreport.

[33]  M. Kiebler,et al.  The GTP-Binding Protein Septin 7 Is Critical for Dendrite Branching and Dendritic-Spine Morphology , 2007, Current Biology.

[34]  S. Schiffmann,et al.  ‘New’ functions for ‘old’ proteins: The role of the calcium-binding proteins calbindin D-28k, calretinin and parvalbumin, in cerebellar physiology. Studies with knockout mice , 2002, The Cerebellum.

[35]  N. Daunton,et al.  Quantitative changes of GABA‐immunoreactive cells in the hindlimb representation of the rat somatosensory cortex after 14‐day hindlimb unloading by tail suspension , 1996, Journal of neuroscience research.

[36]  N. Koibuchi,et al.  Cerebellar Brain-Derived Neurotrophic Factor, Nerve Growth Factor, and Neurotrophin-3 Expression in Male and Female Rats Is Differentially Affected by Hypergravity Exposure During Discrete Developmental Periods , 2009, The Cerebellum.

[37]  Effects of hindlimb unloading on neurogenesis in the hippocampus of newly weaned rats , 2012, Neuroscience Letters.

[38]  E. Alleva,et al.  Cognitive and emotional alterations in periadolescent mice exposed to 2 g hypergravity field , 2004, Physiology & Behavior.

[39]  E. Alleva,et al.  The NGF saga: From animal models of psychosocial stress to stress-related psychopathology , 2009, Frontiers in Neuroendocrinology.

[40]  F Benfenati,et al.  Synaptic vesicle phosphoproteins and regulation of synaptic function. , 1993, Science.

[41]  A. Harmar,et al.  Nerve growth factor regulates expression of neuropeptide genes in adult sensory neurons , 1989, Nature.

[42]  R. Cancedda,et al.  Mice Drawer System: phase c/d development and perspective. , 2002, Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology.

[43]  Jozsef Csicsvari,et al.  Complementary Roles of Cholecystokinin- and Parvalbumin-Expressing GABAergic Neurons in Hippocampal Network Oscillations , 2005, The Journal of Neuroscience.

[44]  E. Alleva,et al.  Aggressive behavior induces release of nerve growth factor from mouse salivary gland into the bloodstream. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[45]  R. Sapolsky,et al.  Glucocorticoids, stress, and their adverse neurological effects: relevance to aging , 1999, Experimental Gerontology.

[46]  Vittorio Cotronei,et al.  The Mice Drawer System (MDS) Experiment and the Space Endurance Record-Breaking Mice , 2012, PloS one.

[47]  H. Thoenen Neurotrophins and Neuronal Plasticity , 1995, Science.

[48]  R. Llinás,et al.  Spaceflight induces changes in the synaptic circuitry of the postnatal developing neocortex. , 2002, Cerebral cortex.

[49]  V R Edgerton,et al.  Myonuclear domain and myosin phenotype in human soleus after bed rest with or without loading. , 1999, Journal of applied physiology.

[50]  Mu-ming Poo,et al.  The neurotrophin hypothesis for synaptic plasticity , 2000, Trends in Neurosciences.

[51]  C. Däpp,et al.  Experimental Physiology - Research Paper A hypoxia complement differentiates the muscle response to endurance exercise , 2012 .

[52]  V R Edgerton,et al.  Sensorimotor adaptations to microgravity in humans. , 2001, The Journal of experimental biology.

[53]  Spatial Learning and Memory Is Preserved in Rats after Early Development in a Microgravity Environment , 2002, Neurobiology of Learning and Memory.