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A Zebrafish Model Of Schizophrenia And Sickness Behavior

Overview

The zebrafish (Danio rerio) has proven to be a solid model vertebrate for genetic screening and is beginning to show promise in disease models as well. This dissertation focuses on the use of the zebrafish for modeling a complex neuropsychiatric disorder, schizophrenia. It also describes preliminary work on a zebrafish Mycobacterium marinum sickness behavior model. Schizophrenia affects approximately 1% of the world's population. Its debilitating symptoms include psychosis, cognitive impairment, and social ...
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Overview

The zebrafish (Danio rerio) has proven to be a solid model vertebrate for genetic screening and is beginning to show promise in disease models as well. This dissertation focuses on the use of the zebrafish for modeling a complex neuropsychiatric disorder, schizophrenia. It also describes preliminary work on a zebrafish Mycobacterium marinum sickness behavior model. Schizophrenia affects approximately 1% of the world's population. Its debilitating symptoms include psychosis, cognitive impairment, and social withdrawal, and its etiology is unknown. An N-methyl-D-aspartate glutamate (NMDA) receptor dysfunction model appears to reliably replicate the full symptom spectrum of schizophrenia. Previous work with zebrafish showed behavioral changes in response to an NMDA receptor antagonist. The shoaling behavior of this highly social species was chosen to evaluate whether social withdrawal could be modeled via exposure to the NMDA receptor antagonist MK-801. Acute exposure to MK-801 significantly disrupted social behavior both at the shoal and pair level. NMDA receptor antagonist exposure reduces anxiety in rodent and primate models. In this zebrafish model, individuals treated with MK-801 similarly showed reduced anxiety, and they appeared to increase locomotor activity. Since NMDA receptor antagonism may be explanatory at the brain mechanism level, this work next investigated a potential endogenous source, kynurenic acid (KYNA). KYNA is an innate immune response byproduct localizable in the brain and other body regions. This pilot work examined zebrafish behavior after KYNA exposure and evaluated social interaction, aggression, and anxiety as part of 'sickness behavior' after exposure to the natural fish pathogen Mycobacterium marinum. No observable alterations in behavior occurred after exposure to KYNA at multiple dose ranges. However, there appeared to be alterations in all three areas of sickness behavior evaluated in the pilot M. marinum study. These observable behavioral modifications may relate to the presence of an endogenous NMDA receptor antagonist. Finally, findings of this work were integrated and potentially profitable lines of future research were discussed. The zebrafish shows tremendous promise as a model organism for investigating wide-ranging hypotheses associated with the complex neuropsychiatric disorder schizophrenia and for studying the bases and performance of sickness behavior.
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Product Details

  • ISBN-13: 9781243731609
  • Publisher: BiblioLabsII
  • Publication date: 9/8/2011
  • Pages: 110
  • Product dimensions: 7.44 (w) x 9.69 (h) x 0.23 (d)

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