Neuropathological Background of MK-801 for Inducing Murine Model of Schizophrenia

  • Ane Murueta-Goyena Larrañaga
  • Arkaitz Bengoetxea Odrioizola
  • Pascual Ángel Gargiulo
  • José Vicente Lafuente Sánchez
Chapter

Abstract

Schizophrenia is a complex psychiatric disorder with a developmental component that compromises neural circuits. Understanding the neuropathological basis of schizophrenia remains a major challenge for establishing new therapeutic approaches. In this review, causal factors for abnormal brain development in schizophrenia are discussed, with particular focus on N-methyl-D-aspartate (NMDA) receptor hypofunction and GABAergic circuit-mediated neurotransmission. Changes in interneuron structure and function have been reported in schizophrenia, and current evidence points to a specific involvement of interneuronal NMDA receptor signaling. Furthermore, altered gamma-band oscillations in schizophrenic patients drew attention to a possible deficit in fast-spiking parvalbumin-expressing interneurons, which play an essential role in regulating complex interaction between pyramidal cells, and represent a key to the understanding of network operations. Here, we describe the major biochemical, neuropathological, and cognitive deficits present in schizophrenic human individuals, and the faithfulness of animal models for mimicking those impairments. In NMDA receptor antagonism-based animal models, repeated injections of MK-801 (dizocilpine) during early postnatal brain development, disrupt the excitation/inhibition balance. A unifying hypothesis to explain the altered brain function in this model is a specific perturbation of GABAergic cells that results in long-term structural brain changes and modified network activity in adulthood, especially when MK-801 is administered during neurodevelopment. Subsequent impairment in cognition, particularly working memory and associative memory, are extremely relevant for schizophrenia research.

Keywords

Schizophrenia MK-801 NMDA Animal model Neurodevelopment 

Notes

Acknowledgements

This study was supported by grants from the University of the Basque Country UPV/EHU (UFI 11/32), (EHU 14/33), and by the Government of the Basque Country (GIC IT 901/16). Murueta-Goyena A is financed by a predoctoral fellowship of the University of the Basque Country (UPV/EHU).

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Ane Murueta-Goyena Larrañaga
    • 1
    • 2
  • Arkaitz Bengoetxea Odrioizola
    • 1
  • Pascual Ángel Gargiulo
    • 3
  • José Vicente Lafuente Sánchez
    • 1
  1. 1.Laboratory of Clinical and Experimental Neurosicence (LaNCE), Department of NeuroscienceUniversity of the Basque Country UPV/EHULeioaSpain
  2. 2.University of the Basque Country, Laboratory of Clinical and Experimental Neuroscience, Department of Neuroscience, Faculty of Medicine and NursingLeioaSpain
  3. 3.Laboratory of Neurosciences and Experimental Psychology, CONICET, Area of Pharmacology, Department of Pathology, Faculty of Medical SciencesNational University of CuyoMendozaArgentina

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