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Gene expression patterns in the hippocampus during the development and aging of Glud1 (Glutamate Dehydrogenase 1) transgenic and wild type mice
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  • 作者：Xinkun Wang (1) (2) (3)
    Nilam D Patel (1)
    Dongwei Hui (1) (3)
    Ranu Pal (1) (3)
    Mohamed M Hafez (4)
    Mohamed M Sayed-Ahmed (4)
    Abdulaziz A Al-Yahya (4) (5)
    Elias K Michaelis (1) (2) (3)
  • 关键词：Brain aging ; Hippocampus ; Glutamate ; Gene expression profile ; Genome
  • 刊名：BMC Neuroscience
  • 出版年：2014
  • 出版时间：December 2014
  • 年：2014
  • 卷：15
  • 期：1
  • 全文大小：797 KB
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  • 作者单位：Xinkun Wang (1) (2) (3)
    Nilam D Patel (1)
    Dongwei Hui (1) (3)
    Ranu Pal (1) (3)
    Mohamed M Hafez (4)
    Mohamed M Sayed-Ahmed (4)
    Abdulaziz A Al-Yahya (4) (5)
    Elias K Michaelis (1) (2) (3)

    1. Higuchi Biosciences Center, University of Kansas, 2099 Constant Ave., Lawrence, KS, 66047, USA
    2. Alzheimer’s Disease Center, University of Kansas Medical Center, Kansas City, KS, 66160, USA
    3. Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS, USA
    4. Department of Pharmacology and Toxicology, School of Pharmacy, King Saud University, Riyadh, Saudi Arabia
    5. Ibn Sina National College, Jeddah, Saudi Arabia
  • ISSN：1471-2202
文摘
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.

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