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Neurogenesis and schizophrenia: dividing neurons in a divided mind?

  • Andreas Reif
  • Angelika Schmitt
  • Sabrina Fritzen
  • Klaus-Peter Lesch
SPECIAL ISSUE

Abstract

Forty years after the initial discovery of neurogenesis in the postnatal brain of the rat, convincing evidence has been accrued that functional neurons are generated throughout the entire lifespan, particularly in the dentate gyrus (DG) and the subventricular zone (SVZ). This phenomenon has been termed adult neurogenesis (AN) and while it was detected in all examined mammalian species including humans, the physiological role of this process remains unknown. Although a plethora of animal studies indicate an involvement of AN in the pathophysiology of depression, this view has recently kindled considerable controversy. Pertinent studies in humans failed to confirm a role of reduced hippocampal neural stem cell proliferation (NSP) in depression but suggest a contribution to the pathophysiology of schizophrenia. The functional relevance of disturbed AN may encompass erroneous temporal encoding of new memory traces, thereby contributing to cognitive deficits observed in schizophrenia. This AN-hypothesis of schizophrenia is supported by neuroimaging, as well as by several genetically modified rodent models, e.g. reelin and NPAS3 knockout mice. Furthermore, several genes impacting on AN, including NPAS3, were also found to be associated with schizophrenia by case-control studies. In conclusion, several lines of evidence suggest that reduced AN may contribute to the etiopathogenesis of schizophrenic disorders, whereas it does not seem to be a critical risk factor for affective disorders.

Keywords

adult neurogenesis schizophrenia candidate genes neuronal stem cell psychiatric disorder postmorten study NPAS3  

Abbreviations

AN

Adult neurogenesis

BDNF

Brain derived neurotrophic factor

BrdU

5-bromo-2-deoxyuridine

DG

Dentate gyrus

DISC1

Disrupted in schizophrenia 1

ECT

Electroconvulsive treatment

FGF-2

Fibroblast growth factor 2

GCL

Granule cell layer

NMDA

N-methyl-D-asparate

NO

Nitric oxide

NOS-I

Nitric oxide synthase type I (neuronal)

NOS-III

Nitric oxide synthase type III (endothelial)

NPAS3

Neuronal PAS domain protein 3

NSP

Neural stem cell proliferation

OB

Olfactory bulb

PCP

Phencyclidine

PPI

Pre-pulse startle inhibition

SGZ

Subgranular zone

SVZ

Subventricular zone

TLE

Temporal lobe epilepsy

VEGF

Vascular endothelial growth factor

Wnt

Wingless-type MMTV integration site family

Wnt 3

Wnt member 3

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Copyright information

© Springer 2007

Authors and Affiliations

  • Andreas Reif
    • 1
  • Angelika Schmitt
    • 1
  • Sabrina Fritzen
    • 1
  • Klaus-Peter Lesch
    • 1
  1. 1.Molecular and Clinical Psychobiology, Department of Psychiatry and PsychotherapyJulius-Maximilians-University WürzburgWürzburgGermany

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