PMID- 28695014
OWN - NLM
STAT- MEDLINE
DCOM- 20180423
LR  - 20181113
IS  - 1687-5443 (Electronic)
IS  - 2090-5904 (Print)
IS  - 1687-5443 (Linking)
VI  - 2017
DP  - 2017
TI  - Impaired Hippocampal Glutamate and Glutamine Metabolism in the db/db Mouse Model 
      of Type 2 Diabetes Mellitus.
PG  - 2107084
LID - 10.1155/2017/2107084 [doi]
LID - 2107084
AB  - Type 2 diabetes mellitus (T2DM) is a risk factor for the development of 
      Alzheimer's disease, and changes in brain energy metabolism have been suggested 
      as a causative mechanism. The aim of this study was to investigate the cerebral 
      metabolism of the important amino acids glutamate and glutamine in the db/db 
      mouse model of T2DM. Glutamate and glutamine are both substrates for 
      mitochondrial oxidation, and oxygen consumption was assessed in isolated brain 
      mitochondria by Seahorse XFe96 analysis. In addition, acutely isolated cerebral 
      cortical and hippocampal slices were incubated with [U-(13)C]glutamate and 
      [U-(13)C]glutamine, and tissue extracts were analyzed by gas chromatography-mass 
      spectrometry. The oxygen consumption rate using glutamate and glutamine as 
      substrates was not different in isolated cerebral mitochondria of db/db mice 
      compared to controls. Hippocampal slices of db/db mice exhibited significantly 
      reduced (13)C labeling in glutamate, glutamine, GABA, citrate, and aspartate from 
      metabolism of [U-(13)C]glutamate. Additionally, reduced (13)C labeling were 
      observed in GABA, citrate, and aspartate from [U-(13)C]glutamine metabolism in 
      hippocampal slices of db/db mice when compared to controls. None of these changes 
      were observed in cerebral cortical slices. The results suggest specific 
      hippocampal impairments in glutamate and glutamine metabolism, without affecting 
      mitochondrial oxidation of these substrates, in the db/db mouse.
FAU - Andersen, Jens Velde
AU  - Andersen JV
AD  - Department of Drug Design and Pharmacology, Faculty of Health and Medical 
      Sciences, University of Copenhagen, Copenhagen, Denmark.
FAU - Nissen, Jakob Dahl
AU  - Nissen JD
AD  - Department of Drug Design and Pharmacology, Faculty of Health and Medical 
      Sciences, University of Copenhagen, Copenhagen, Denmark.
FAU - Christensen, Sofie Kjellerup
AU  - Christensen SK
AD  - Department of Drug Design and Pharmacology, Faculty of Health and Medical 
      Sciences, University of Copenhagen, Copenhagen, Denmark.
FAU - Markussen, Kia Hjulmand
AU  - Markussen KH
AD  - Department of Drug Design and Pharmacology, Faculty of Health and Medical 
      Sciences, University of Copenhagen, Copenhagen, Denmark.
FAU - Waagepetersen, Helle Sonderby
AU  - Waagepetersen HS
AUID- ORCID: 0000-0003-4583-8379
AD  - Department of Drug Design and Pharmacology, Faculty of Health and Medical 
      Sciences, University of Copenhagen, Copenhagen, Denmark.
LA  - eng
PT  - Journal Article
DEP - 20170614
PL  - United States
TA  - Neural Plast
JT  - Neural plasticity
JID - 100883417
RN  - 0RH81L854J (Glutamine)
RN  - 3KX376GY7L (Glutamic Acid)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Glutamic Acid/*metabolism
MH  - Glutamine/*metabolism
MH  - Hippocampus/*metabolism
MH  - Mice
MH  - Mitochondria/metabolism
MH  - Oxygen Consumption/physiology
PMC - PMC5488168
EDAT- 2017/07/12 06:00
MHDA- 2018/04/24 06:00
PMCR- 2017/06/14
CRDT- 2017/07/12 06:00
PHST- 2017/02/27 00:00 [received]
PHST- 2017/04/10 00:00 [accepted]
PHST- 2017/07/12 06:00 [entrez]
PHST- 2017/07/12 06:00 [pubmed]
PHST- 2018/04/24 06:00 [medline]
PHST- 2017/06/14 00:00 [pmc-release]
AID - 10.1155/2017/2107084 [doi]
PST - ppublish
SO  - Neural Plast. 2017;2017:2107084. doi: 10.1155/2017/2107084. Epub 2017 Jun 14.