Conditional Knockout of GLT-1 in Neurons Leads to Alterations in Aspartate Homeostasis and Synaptic Mitochondrial Metabolism in Striatum and Hippocampus.

Neurochemical Research
Laura F McNairBlanca I Aldana

Abstract

Expression of the glutamate transporter GLT-1 in neurons has been shown to be important for synaptic mitochondrial function in the cerebral cortex. Here we determined whether neuronal GLT-1 plays a similar role in the hippocampus and striatum, using conditional GLT-1 knockout mice in which GLT-1 was inactivated in neurons by expression of synapsin-Cre (synGLT-1 KO). Ex vivo 13C-labelling using [1,2-13C]acetate, representing astrocytic metabolism, yielded increased [4,5-13C]glutamate levels, suggesting increased astrocyte-neuron glutamine transfer, in the striatum but not in the hippocampus of the synGLT-1 KO. Moreover, aspartate concentrations were reduced - 38% compared to controls in the hippocampus and the striatum of the synGLT-1 KO. Mitochondria isolated from the hippocampus of synGLT-1 KO mice exhibited a lower oxygen consumption rate in the presence of oligomycin A, indicative of a decreased proton leak across the mitochondrial membrane, whereas the ATP production rate was unchanged. Electron microscopy revealed reduced mitochondrial inter-cristae distance within excitatory synaptic terminals in the hippocampus and striatum of the synGLT-1 KO. Finally, dilution of 13C-labelling originating from [U-13C]glucose, caused by ...Continue Reading

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Citations

Nov 8, 2020·Neurochemistry International·Kathryn D FischerPaul A Rosenberg
Apr 28, 2021·Neurochemical Research·Niels Christian DanboltYun Zhou
May 1, 2021·Frontiers in Cellular Neuroscience·Renae M RyanAnnalisa Scimemi
Jul 18, 2021·Neuropharmacology·Jens V AndersenBlanca I Aldana

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Methods Mentioned

BETA
electron microscopy
Nuclear Magnetic Resonance
protein assay

Software Mentioned

TopSpin
ROUT
ImageJ
Wave
Prism
GraphPad

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