Immature dentate gyrus as a candidate endophenotype of psychiatric disorders

Keizo Takao, Tsuyoshi Miyakawa

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Despite massive research efforts, the exact pathogenesis and pathophysiology of psychiatric disorders, such as schizophrenia and bipolar disorder, remain largely unknown. Animal models can serve as essential tools for investigating the etiology and treatment of such disorders. Some mutant mouse strains were found to exhibit behavioral abnormalities reminiscent of human psychiatric disorders. Here we outline our unique approach of extrapolating findings in mice to humans, and present studies on alpha-CaMKII heterozygous knockout (alpha-CaMKII HKO) mice as examples. Alpha-CaMKII HKO mice have profoundly dysregulated behavior and impaired neuronal development in the dentate gyrus (DG). The behavioral abnormalities include a severe working memory deficit and an exaggerated infradian rhythm, which are similar to symptoms seen in schizophrenia, bipolar mood disorder and other psychiatric disorders. By conducting a series of experiments, we discovered that almost all the neurons in the mutant DG were very similar to the immature DG neurons of normal rodents. In other words, alpha-CaMKII HKO mice have an "immature DG". We proposed that an "immature DG" in adulthood might induce alterations in behavior and serve as a promising candidate endophenotype of schizophrenia and other human psychiatric disorders.

Original languageEnglish
Pages (from-to)115-122
Number of pages8
JournalJapanese Journal of Neuropsychopharmacology
Volume30
Issue number3
Publication statusPublished - 01-06-2010

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Endophenotypes
Dentate Gyrus
Psychiatry
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Schizophrenia
Bipolar Disorder
Knockout Mice
Mutant Strains Mice
Neurons
Memory Disorders
Mood Disorders
Short-Term Memory
Rodentia
Animal Models
Research

All Science Journal Classification (ASJC) codes

  • Clinical Psychology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

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Immature dentate gyrus as a candidate endophenotype of psychiatric disorders. / Takao, Keizo; Miyakawa, Tsuyoshi.

In: Japanese Journal of Neuropsychopharmacology, Vol. 30, No. 3, 01.06.2010, p. 115-122.

Research output: Contribution to journalReview article

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