Neuron-specific deficits of bioenergetic processes in the dorsolateral prefrontal cortex in schizophrenia.
Adult
Brain
/ metabolism
Energy Metabolism
Female
Glucose Transporter Type 1
/ metabolism
Glucose Transporter Type 3
/ metabolism
Hexokinase
/ analysis
Humans
Laser Capture Microdissection
Male
Middle Aged
Monocarboxylic Acid Transporters
/ metabolism
Neurons
/ metabolism
Phosphofructokinase-1
/ analysis
Prefrontal Cortex
/ metabolism
Pyramidal Cells
/ metabolism
RNA, Messenger
/ metabolism
Schizophrenia
/ genetics
Signal Transduction
/ physiology
Symporters
/ metabolism
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
18
08
2017
accepted:
15
01
2018
revised:
07
12
2017
pubmed:
3
3
2018
medline:
28
4
2020
entrez:
3
3
2018
Statut:
ppublish
Résumé
Schizophrenia is a devastating illness that affects over 2 million people in the United States and costs society billions of dollars annually. New insights into the pathophysiology of schizophrenia are needed to provide the conceptual framework to facilitate development of new treatment strategies. We examined bioenergetic pathways in the dorsolateral prefrontal cortex (DLPFC) of subjects with schizophrenia and control subjects using western blot analysis, quantitative real-time polymerase chain reaction, and enzyme/substrate assays. Laser-capture microdissection-quantitative polymerase chain reaction was used to examine these pathways at the cellular level. We found decreases in hexokinase (HXK) and phosphofructokinase (PFK) activity in the DLPFC, as well as decreased PFK1 mRNA expression. In pyramidal neurons, we found an increase in monocarboxylate transporter 1 mRNA expression, and decreases in HXK1, PFK1, glucose transporter 1 (GLUT1), and GLUT3 mRNA expression. These results suggest abnormal bioenergetic function, as well as a neuron-specific defect in glucose utilization, in the DLPFC in schizophrenia.
Identifiants
pubmed: 29497148
doi: 10.1038/s41380-018-0035-3
pii: 10.1038/s41380-018-0035-3
pmc: PMC6119539
mid: NIHMS935052
doi:
Substances chimiques
Glucose Transporter Type 1
0
Glucose Transporter Type 3
0
Monocarboxylic Acid Transporters
0
RNA, Messenger
0
SLC2A1 protein, human
0
SLC2A3 protein, human
0
Symporters
0
monocarboxylate transport protein 1
0
Hexokinase
EC 2.7.1.1
Phosphofructokinase-1
EC 2.7.1.11
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1319-1328Subventions
Organisme : NIMH NIH HHS
ID : R01 MH094445
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH107487
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH107916
Pays : United States
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