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Structural and functional neuroimaging phenotypes in dysbindin mutant mice.

Evan Lutkenhoff1, Katherine H Karlsgodt, Boris Gutman

  • 1Interdisciplinary Neuroscience Program, University of California, Los Angeles, CA 90095, USA.

Neuroimage
|May 16, 2012
PubMed
Summary

Dysbindin-1 gene deletion in mice alters brain function and structure, particularly in dopamine-rich and auditory regions. These findings offer insights into schizophrenia endophenotypes and the role of dysbindin-1 in brain health.

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Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • Schizophrenia is a highly heritable psychiatric disorder linked to brain structural and functional abnormalities.
  • The DTNBP1 gene, encoding dysbindin-1, is a key candidate gene for schizophrenia.
  • Investigating dysbindin-1 in isolation is crucial for understanding its role in schizophrenia.

Purpose of the Study:

  • To explore regional brain alterations in structure and function caused by the loss of the dysbindin-1 gene.
  • To utilize a mouse model with a specific genomic deletion in the dysbindin gene for isolated gene study.
  • To apply manganese-enhanced magnetic resonance imaging (MEMRI) and tensor-based morphometry for comprehensive analysis.

Main Methods:

  • Manganese-enhanced magnetic resonance imaging (MEMRI) to assess regional brain activity over 24 hours.

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  • Analysis of manganese uptake rates to infer basal cellular activity in specific brain regions.
  • Tensor-based morphometry applied to MRI data to detect structural volume changes.

    • Main Results:

    • Significant differences in manganese uptake were observed in dopamine-rich brain regions and hippocampal subregions (CA1, dentate gyrus).
    • Structural volume deficits were identified in cortical regions (especially auditory cortex), subiculum, dentate gyrus, and striatum of dysbindin mutant mice.
    • The study revealed both expected and novel structural and functional neural alterations linked to dysbindin-1.

    Conclusions:

    • Loss of dysbindin-1 leads to specific structural and functional brain alterations relevant to schizophrenia.
    • This research is the first to apply MEMRI to a mouse model of schizophrenia endophenotypes, combining functional and structural imaging.
    • Findings enhance the understanding of dysbindin-1's role in neural pathways implicated in schizophrenia.