Immature dentate gyrus: An endophenotype of neuropsychiatric disorders

Hideo Hagihara, Keizo Takao, Noah M. Walton, Mitsuyuki Matsumoto, Tsuyoshi Miyakawa

Research output: Contribution to journalReview article

61 Citations (Scopus)

Abstract

Adequate maturation of neurons and their integration into the hippocampal circuit is crucial for normal cognitive function and emotional behavior, and disruption of this process could cause disturbances in mental health. Previous reports have shown that mice heterozygous for a null mutation in -CaMKII, which encodes a key synaptic plasticity molecule, display abnormal behaviors related to schizophrenia and other psychiatric disorders. In these mutants, almost all neurons in the dentate gyrus are arrested at a pseudoimmature state at the molecular and electrophysiological levels, a phenomenon defined as "immature dentate gyrus (iDG)." To date, the iDG phenotype and shared behavioral abnormalities (including working memory deficit and hyperlocomotor activity) have been discovered in Schnurri-2 knockout, mutant SNAP-25 knock-in, and forebrain-specific calcineurin knockout mice. In addition, both chronic fluoxetine treatment and pilocarpine-induced seizures reverse the neuronal maturation, resulting in the iDG phenotype in wild-type mice. Importantly, an iDG-like phenomenon was observed in post-mortem analysis of brains from patients with schizophrenia/bipolar disorder. Based on these observations, we proposed that the iDG is a potential endophenotype shared by certain types of neuropsychiatric disorders. This review summarizes recent data describing this phenotype and discusses the data's potential implication in elucidating the pathophysiology of neuropsychiatric disorders.

Original languageEnglish
Article number318596
JournalNeural Plasticity
Volume2013
DOIs
Publication statusPublished - 01-01-2013

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Endophenotypes
Dentate Gyrus
Phenotype
Schizophrenia
Neurons
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Neuronal Plasticity
Pilocarpine
Calcineurin
Fluoxetine
Memory Disorders
Prosencephalon
Bipolar Disorder
Short-Term Memory
Knockout Mice
Cognition
Psychiatry
Mental Health
Seizures
Mutation

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

Hagihara, Hideo ; Takao, Keizo ; Walton, Noah M. ; Matsumoto, Mitsuyuki ; Miyakawa, Tsuyoshi. / Immature dentate gyrus : An endophenotype of neuropsychiatric disorders. In: Neural Plasticity. 2013 ; Vol. 2013.
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Immature dentate gyrus : An endophenotype of neuropsychiatric disorders. / Hagihara, Hideo; Takao, Keizo; Walton, Noah M.; Matsumoto, Mitsuyuki; Miyakawa, Tsuyoshi.

In: Neural Plasticity, Vol. 2013, 318596, 01.01.2013.

Research output: Contribution to journalReview article

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