title: Gene expression patterns in the hippocampus during the development and aging of Glud1 (Glutamate Dehydrogenase 1) transgenic and wild type mice.
abstract: BACKGROUND
  Extraneuronal levels of the neurotransmitter glutamate in brain rise during aging. This is thought to lead to synaptic dysfunction and neuronal injury or death. To study the effects of glutamate hyperactivity in brain, we created transgenic (Tg) mice in which the gene for glutamate dehydrogenase (Glud1) is over-expressed in neurons and in which such overexpression leads to excess synaptic release of glutamate. In this study, we analyzed whole genome expression in the hippocampus, a region important for learning and memory, of 10 day to 20 month old Glud1 and wild type (wt) mice.
  
  
  RESULTS
  During development, maturation and aging, both Tg and wt exhibited decreases in the expression of genes related to neurogenesis, neuronal migration, growth, and process elongation, and increases in genes related to neuro-inflammation, voltage-gated channel activity, and regulation of synaptic transmission. Categories of genes that were differentially expressed in Tg vs. wt during development were: synaptic function, cytoskeleton, protein ubiquitination, and mitochondria; and, those differentially expressed during aging were: synaptic function, vesicle transport, calcium signaling, protein kinase activity, cytoskeleton, neuron projection, mitochondria, and protein ubiquitination. Overall, the effects of Glud1 overexpression on the hippocampus transcriptome were greater in the mature and aged than the young.
  
  
  CONCLUSIONS
  Glutamate hyperactivity caused gene expression changes in the hippocampus at all ages. Some of these changes may result in premature brain aging. The identification of these genomic expression differences is important in understanding the effects of glutamate dysregulation on neuronal function during aging or in neurodegenerative diseases.
authors.affiliation: Higuchi Biosciences Center, University of Kansas, 2099 Constant Ave,, Lawrence, KS 66047, USA. xwang@ku.edu.
authors.forename: Xinkun
authors.initials: X
authors.lastname: Wang
authors.forename: Nilam D
authors.initials: ND
authors.lastname: Patel
authors.forename: Dongwei
authors.initials: D
authors.lastname: Hui
authors.forename: Ranu
authors.initials: R
authors.lastname: Pal
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Hafez
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Sayed-Ahmed
authors.forename: Abdulaziz A
authors.initials: AA
authors.lastname: Al-Yahya
authors.forename: Elias K
authors.initials: EK
authors.lastname: Michaelis
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005969:Glutamate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism*; D014018:Tissue Distribution; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D009419:Nerve Tissue Proteins; D020543:Proteome; D018698:Glutamic Acid; D005969:Glutamate Dehydrogenase; C561840:GLUD1 protein, human