Stable isotope tracing reveals disturbed cellular energy and glutamate metabolism in hippocampal slices of aged male mice
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Stable isotope tracing reveals disturbed cellular energy and glutamate metabolism in hippocampal slices of aged male mice. / McNair, Laura Mikél; Andersen, Jens Velde; Waagepetersen, Helle Sønderby.
In: Neurochemistry International, Vol. 171, 105626, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Stable isotope tracing reveals disturbed cellular energy and glutamate metabolism in hippocampal slices of aged male mice
AU - McNair, Laura Mikél
AU - Andersen, Jens Velde
AU - Waagepetersen, Helle Sønderby
N1 - Publisher Copyright: © 2023 The Authors
PY - 2023
Y1 - 2023
N2 - Neurons and astrocytes work in close metabolic collaboration, linking neurotransmission to brain energy and neurotransmitter metabolism. Dysregulated energy metabolism is a hallmark of the aging brain and may underlie the progressive age-dependent cognitive decline. However, astrocyte and neurotransmitter metabolism remains understudied in aging brain research. In particular, how aging affects metabolism of glutamate, being the primary excitatory neurotransmitter, is still poorly understood. Here we investigated critical aspects of cellular energy metabolism in the aging male mouse hippocampus using stable isotope tracing in vitro. Metabolism of [U–13C]glucose demonstrated an elevated glycolytic capacity of aged hippocampal slices, whereas oxidative [U–13C]glucose metabolism in the TCA cycle was significantly reduced with aging. In addition, metabolism of [1,2–13C]acetate, reflecting astrocyte energy metabolism, was likewise reduced in the hippocampal slices of old mice. In contrast, uptake and subsequent metabolism of [U–13C]glutamate was elevated, suggesting increased capacity for cellular glutamate handling with aging. Finally, metabolism of [15N]glutamate was maintained in the aged slices, demonstrating sustained glutamate nitrogen metabolism. Collectively, this study reveals fundamental alterations in cellular energy and neurotransmitter metabolism in the aging brain, which may contribute to age-related hippocampal deficits.
AB - Neurons and astrocytes work in close metabolic collaboration, linking neurotransmission to brain energy and neurotransmitter metabolism. Dysregulated energy metabolism is a hallmark of the aging brain and may underlie the progressive age-dependent cognitive decline. However, astrocyte and neurotransmitter metabolism remains understudied in aging brain research. In particular, how aging affects metabolism of glutamate, being the primary excitatory neurotransmitter, is still poorly understood. Here we investigated critical aspects of cellular energy metabolism in the aging male mouse hippocampus using stable isotope tracing in vitro. Metabolism of [U–13C]glucose demonstrated an elevated glycolytic capacity of aged hippocampal slices, whereas oxidative [U–13C]glucose metabolism in the TCA cycle was significantly reduced with aging. In addition, metabolism of [1,2–13C]acetate, reflecting astrocyte energy metabolism, was likewise reduced in the hippocampal slices of old mice. In contrast, uptake and subsequent metabolism of [U–13C]glutamate was elevated, suggesting increased capacity for cellular glutamate handling with aging. Finally, metabolism of [15N]glutamate was maintained in the aged slices, demonstrating sustained glutamate nitrogen metabolism. Collectively, this study reveals fundamental alterations in cellular energy and neurotransmitter metabolism in the aging brain, which may contribute to age-related hippocampal deficits.
KW - Astrocytes
KW - Glutamate uptake
KW - Glutamate-glutamine cycle
KW - Isotope tracing
U2 - 10.1016/j.neuint.2023.105626
DO - 10.1016/j.neuint.2023.105626
M3 - Journal article
C2 - 37838084
AN - SCOPUS:85174348073
VL - 171
JO - Neurochemistry International
JF - Neurochemistry International
SN - 0197-0186
M1 - 105626
ER -
ID: 373613025