Gene expression patterns in the hippocampus during the development and aging of Glud1 (Glutamate Dehydrogenase 1) transgenic and wild type mice

BMC Neuroscience

Elias K Michaelis²  Abdulaziz A Al-Yahya¹  Mohamed M Sayed-Ahmed⁴  Mohamed M Hafez⁴  Ranu Pal²  Dongwei Hui²  Nilam D Patel³  Xinkun Wang² 

[1] Ibn Sina National College, Jeddah, Saudi Arabia;Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS, USA;Higuchi Biosciences Center, University of Kansas, 2099 Constant Ave., Lawrence, KS 66047, USA;Department of Pharmacology and Toxicology, School of Pharmacy, King Saud University, Riyadh, Saudi Arabia

关键词: Genome;    Gene expression profile;    Glutamate;    Hippocampus;    Brain aging;   

Others  :  1092060
DOI  :  10.1186/1471-2202-15-37

 received in 2013-07-17, accepted in 2014-02-24,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Wang et al.; licensee BioMed Central Ltd.

【 图 表 】

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