MK-801 treatment affects glycolysis in oligodendrocytes more than in astrocytes and neuronal cells: insights for schizophrenia

Author(s)

Guest, Paul C. ^[1] ; Iwata, Keiko ^{[2, 3]} ; Kato, Takahiro A. ^{[4, 5]} ; Steiner, Johann ^[6] ; Schmitt, Andrea ^{[7, 8]} ; Turck, Christoph W. ^[9] ; Martins-de-Souza, Daniel ^{[1, 8, 10]}

Affiliation

^[1] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, Lab Neuroprote, BR-13083862 Campinas, SP - Brazil

^[2] Univ Fukui, Res Ctr Child Mental Dev, Fukui 910 - Japan

^[3] Univ Fukui, Chiba Univ, Hamamatsu Univ Sch Med, Dept Dev Funct Brain Act, Kanazawa Univ, Osaka Univ, United Grad Sch Child De, Fukui 910 - Japan

^[4] Kyushu Univ, Grad Sch Med Sci, Dept Neuropsychiat, Fukuoka 812 - Japan

^[5] Kyushu Univ, Innovat Ctr Med Redox Nav, Fukuoka 812 - Japan

^[6] Univ Magdeburg, Ctr Behav Brain Sci, Dept Psychiat & Psychotherapy, D-39106 Magdeburg - Germany

^[7] Univ Munich, Dept Psychiat & Psychotherapy, Munich - Germany

^[8] Univ Sao Paulo, Inst Psychiat, Lab Neurosci LIM 27, Sao Paulo - Brazil

^[9] Max Planck Inst Psychiat, Dept Translat Res Psychiat Prote & Biomarkers, D-80804 Munich - Germany

^[10] UNICAMPs Neurobiol Ctr, Campinas, SP - Brazil

• Document type: Journal article
• Source: FRONTIERS IN CELLULAR NEUROSCIENCE; v. 9, MAY 12 2015.
• Web of Science Citations: 19

Abstract

Schizophrenia is a debilitating mental disorder, affecting more than 30 million people worldwide. As a multifactorial disease, the underlying causes of schizophrenia require analysis by multiplex methods such as proteomics to allow identification of whole protein networks. Previous post-mortem proteomic studies on brain tissues from schizophrenia patients have demonstrated changes in activation of glycolytic and energy metabolism pathways. However, it is not known whether these changes occur in neurons or in glial cells. To address this question, we treated neuronal, astrocyte, and oligodendrocyte cell lines with the NMDA receptor antagonist MK-801 and measured the levels of six glycolytic enzymes by Western blot analysis. MK-801 acts on the glutamatergic system and has been proposed as a pharmacological means of modeling schizophrenia. Treatment with MK-801 resulted in significant changes in the levels of glycolytic enzymes in all cell types. Most of the differences were found in oligodendrocytes, which had altered levels of hexokinase 1 (HK1), enolase 2 (ENO2), phosphoglycerate kinase (PG, and phosphoglycerate mutase 1 after acute MK-801 treatment (8 h), and HK1, ENO2, PGK, and triosephosphate isomerase (TPI) following long term treatment (72 h). Addition of the antipsychotic clozapine to the cultures resulted in counter-regulatory effects to the MK-801 treatment by normalizing the levels of ENO2 and PGK in both the acute and long term cultures. In astrocytes, MK-801 affected only aldolase C (ALDOC) under both acute conditions and HK1 and ALDOC following long term treatment, and TPI was the only enzyme affected under long term conditions in the neuronal cells. In conclusion, MK-801 affects glycolysis in oligodendrocytes to a larger extent than neuronal cells and this may be modulated by antipsychotic treatment. Although cell culture studies do not necessarily reflect the in vivo pathophysiology and drug effects within the brain, these results suggest that neurons, astrocytes, and oligodendrocytes are affected differently in schizophrenia. Employing in vitro models using neurotransmitter agonists and antagonists may provide new insights about the pathophysiology of schizophrenia which could lead to a novel system for drug discovery. (AU)

• FAPESP's process: 13/08711-3 - Developing a predictive test for a successful medication response and understanding the molecular bases of schizophrenia through proteomics
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Research Grants - Young Investigators Grants