Metabolism changes during aging in the hippocampus and striatum of glud1 (glutamate dehydrogenase 1) transgenic mice.
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 ((1)H) 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.
Hoglund Brain Imaging Center, University of Kansas Medical Center, Kansas City, KS, USA.
In-Young
IY
Choi
Phil
P
Lee
Wen-Tung
WT
Wang
Dongwei
D
Hui
Xinkun
X
Wang
William M
WM
Brooks
Elias K
EK
Michaelis
D000375:Aging; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D005969:Glutamate Dehydrogenase; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
D017470:Receptors, Glutamate; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate; C570817:GluD1 protein, mouse; D005969:Glutamate Dehydrogenase