Calcineurin knockout mice show a selective loss of small spines

Hitoshi Okazaki1, Akiko Hayashi-Takagi2, Akira Nagaoka3

  • 1Laboratory of Structural Physiology, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan; International Research Center for Neurointelligence (WPI-IRCN), UTIAS, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Neuroscience Letters
|February 11, 2018
PubMed

Insights

Calcineurin B knockout mice show altered dendritic spine size, mirroring changes seen in schizophrenia patients. This suggests a potential role for calcineurin in the neurobiology of schizophrenia.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Psychiatry

Background:

  • Calcineurin is crucial for synaptic plasticity, including long-term depression and spine shrinkage.
  • Calcineurin mutations are linked to schizophrenia, and related mouse models display behavioral deficits.
  • The impact of calcineurin deficiency on dendritic spine morphology in these models remains unexamined.

Purpose of the Study:

  • To investigate the dendritic spine phenotype in mice with conditional knockout of calcineurin B (CNB-KO).
  • To determine if CNB-KO mice exhibit spine alterations relevant to schizophrenia.

Main Methods:

  • Examined dendritic spines in the prefrontal and visual cortices of CNB-KO mice.
  • Quantified spine size distribution and compared it to wild-type controls.

Main Results:

  • CNB-KO mice displayed a significant reduction in small dendritic spines.
  • An increase in large dendritic spines was observed in the prefrontal and visual cortices of CNB-KO mice.
  • The observed spine phenotype was moderate, potentially influenced by spine dynamics.

Conclusions:

  • CNB-KO mice exhibit a dendritic spine phenotype resembling that reported in schizophrenia patients.
  • These findings support a role for calcineurin in the structural changes of dendritic spines associated with schizophrenia.
  • CNB-KO mice serve as a valuable model for studying the neurobiological underpinnings of schizophrenia.

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