Gene expression patterns in the hippocampus during the development and aging of Glud1 (Glutamate Dehydrogenase 1) transgenic and wild type mice
Issue Date
2014-03-04Author
Wang, Xinkun
Patel, Nilam D.
Hui, Dongwei
Pal, Ranu
Hafez, Mohamed M.
Sayed-Ahmed, Mohamed M.
Al-Yahya, Abdulaziz A.
Michaelis, Elias K.
Publisher
BMC Neuroscience
Type
Article
Article Version
Scholarly/refereed, publisher version
Rights
Copyright ©2012 Optical Society of America. The author may also publish the article on his or her own noncommercial web page ("noncommercial" pages are defined here as those not charging for admission to the site or for downloading of material while on the site).
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Show full item recordAbstract
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.
Description
A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author’s publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.
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Citation
Wang, Xinkun., Patel, Nilam D., Hui, Dongwei., Pal, Ranu., Hafez, Mohamed M., Sayed-Ahmed, Mohamed M., Al-Yahya, Abdulaziz A., Michaelis, Elias K. "Gene expression patterns in the hippocampus during the development and aging of Glud1 (Glutamate Dehydrogenase 1) transgenic and wild type mice." (2014) BMC Neuroscience 2014, 15:37. http://dx.doi.org/10.1186/1471-2202-15-37.
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