Linking proteomic alterations in schizophrenia hippocampus to NMDAr hypofunction in human neurons and oligodendrocytes

Eur Arch Psychiatry Clin Neurosci. 2021 Dec;271(8):1579-1586. doi: 10.1007/s00406-021-01248-w. Epub 2021 Mar 10.

Abstract

Glutamatergic neurotransmission dysfunction and the early involvement of the hippocampus have been proposed to be important aspects of the pathophysiology of schizophrenia. Here, we performed proteomic analysis of hippocampus postmortem samples from schizophrenia patients as well as neural cells-neurons and oligodendrocytes-treated with MK-801, an NMDA receptor antagonist. There were similarities in processes such as oxidative stress and apoptotic process when comparing hippocampus samples with MK-801-treated neurons, and in proteins synthesis when comparing hippocampus samples with MK-801-treated oligodendrocytes. This reveals that studying the effects of glutamatergic dysfunction in different neural cells can contribute to a better understanding of what it is observed in schizophrenia patients' postmortem brains.

Keywords: Hippocampus; MK-801; Neurons; Oligodendrocytes; Proteome.

MeSH terms

  • Dizocilpine Maleate / therapeutic use
  • Hippocampus* / metabolism
  • Humans
  • Neurons
  • Oligodendroglia
  • Proteomics
  • Receptors, N-Methyl-D-Aspartate* / physiology
  • Schizophrenia* / metabolism

Substances

  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate