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

MURUETA-GOYENA-LARRAÑAGA, A.; BENGOTXEA, H.; ; GARGIULO, P.A. ; ORTUZAR, N. ; LAFUENTE, J.V.

Psychiatry and Neurosciences. Translational Approaches. Gargiulo, P.A. and Mesones, H.L. (Editors). Springer New York. New York 2016. (ISBN: 978-3-319-53125-0).-

Springer

Lugar: New York / Zurich; Año: 2017; p. 337 - 354

Neuropathological background of MK801 for inducing murine model of schizophrenia. Murueta-Goyena-Larrañaga, A.; Bengotxea, H.; Gargiulo, P.A.; Ortuzar, N.; Lafuente, J.V. En: ?Psychiatry and Neurosciences. Translational Approaches.? Gargiulo, P.A. and Mesones, H.L. (Editors). Springer New York. New York 2017. (ISBN: 978-3-319-53125-0).-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 NMDA receptor hypofunction and GABAergic circuit-mediated neurotransmission. Changes in interneuron structure and function have been reported in schizophrenia, and current evidences point out 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 N-methyl-D-aspartate (NMDA) receptor antagonism based animal models, repeated injections of MK801 (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 MK801 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