Neurochemical Research

, Volume 39, Issue 3, pp 446–455 | Cite as

Metabolism Changes During Aging in the Hippocampus and Striatum of Glud1 (Glutamate Dehydrogenase 1) Transgenic Mice

  • In-Young Choi
  • Phil Lee
  • Wen-Tung Wang
  • Dongwei Hui
  • Xinkun Wang
  • William M. Brooks
  • Elias K. Michaelis
Original Paper


The decline in neuronal function during aging may result from increases in extracellular glutamate (Glu), Glu-induced neurotoxicity, and altered mitochondrial metabolism. To study metabolic responses to persistently high levels of Glu at synapses during aging, we used transgenic (Tg) mice that over-express the enzyme Glu dehydrogenase (GDH) in brain neurons and release excess Glu in synapses. Mitochondrial GDH is important in amino acid and carbohydrate metabolism and in anaplerotic reactions. We monitored changes in nineteen neurochemicals in the hippocampus and striatum of adult, middle aged, and aged Tg and wild type (wt) mice, in vivo, using proton (1H) magnetic resonance spectroscopy. Significant differences between adult Tg and wt were higher Glu, N-acetyl aspartate (NAA), and NAA + NAA–Glu (NAAG) levels, and lower lactate in the Tg hippocampus and striatum than those of wt. During aging, consistent changes in Tg and wt hippocampus and striatum included increases in myo-inositol and NAAG. The levels of glutamine (Gln), a key neurochemical in the Gln-Glu cycle between neurons and astroglia, increased during aging in both the striatum and hippocampus of Tg mice, but only in the striatum of the wt mice. Age-related increases of Glu were observed only in the striatum of the Tg mice.


Brain metabolism Hippocampus Striatum Magnetic resonance spectroscopy 



This work was funded by grants from the National Institutes of Health, NIA: AG12993 and AG035982; and NICHD: HD02528. The support of the Higuchi Biosciences Center and of the Hoglund Brain Imaging Center at the University of Kansas is acknowledged.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • In-Young Choi
    • 1
    • 2
    • 3
  • Phil Lee
    • 1
    • 3
  • Wen-Tung Wang
    • 1
  • Dongwei Hui
    • 4
    • 5
  • Xinkun Wang
    • 4
    • 5
  • William M. Brooks
    • 1
    • 2
  • Elias K. Michaelis
    • 4
    • 5
  1. 1.Hoglund Brain Imaging CenterUniversity of Kansas Medical CenterKansas CityUSA
  2. 2.Department of NeurologyUniversity of Kansas Medical CenterKansas CityUSA
  3. 3.Department of Molecular and Integrative PhysiologyUniversity of Kansas Medical CenterKansas CityUSA
  4. 4.Higuchi Biosciences CenterUniversity of KansasLawrenceUSA
  5. 5.Department of Pharmacology and ToxicologyUniversity of KansasLawrenceUSA

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