Neuron-specific deficits of bioenergetic processes in the dorsolateral prefrontal cortex in schizophrenia

Molecular Psychiatry
Courtney R SullivanRobert E McCullumsmith

Abstract

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.

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Citations

Oct 20, 2018·Molecular Neurobiology·Courtney R SullivanRobert E McCullumsmith
Oct 28, 2019·EMBO Molecular Medicine·Masayuki IdeTakeo Yoshikawa
Apr 28, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Peiyan Ni, Sangmi Chung
Nov 16, 2019·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Masoumeh DehghaniLijing Xin
Feb 19, 2020·Translational Psychiatry·Anita L PinnerJames H Meador-Woodruff
Jul 1, 2020·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Rammohan ShuklaRobert E Mccullumsmith
Feb 9, 2021·Schizophrenia Bulletin Open·Cagri YukselFei Du
Jun 10, 2020·Schizophrenia Research·Tommaso ZeppilloMarquis P Vawter
Nov 26, 2021·Bioscience Reports·Gabriela Assis-de-LemosAntonio Galina

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Methods Mentioned

BETA
laser-capture microdissection

Software Mentioned

Statistica

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