Background
Growing evidence implicates abnormal neurodevelopment in schizophrenia, which manifests
itself, for example, in reduced volume and cellular disarray of the hippocampus. This
prompted us to investigate if there are indications of an altered neurodevelopment
in this brain region. While neuron birth is largely completed by the end of gestation,
granule neurons of the dentate gyrus are generated throughout life, thus offering
an opportunity to investigate neurogenesis postnatally.
Methods
We investigated whether repeated application of subanesthetic doses of the noncompetitive
N-methyl-D-aspartate receptor antagonist ketamine, which has been shown to mimic model
aspects of schizophrenia in animals, affects the hippocampal neurogenesis detected
by bromodeoxyuridine incorporation. Cells were identified by immunocytochemistry.
Results
Subanesthetic doses of ketamine applied subchronically enhance neurogenesis in the
hippocampal subgranular zone.
Conclusions
In our animal model of schizophrenia, ketamine may evoke its stimulating effect on
neurogenesis via a block of the N-methyl-D-aspartate receptor directly by reducing
the c-Fos/c-Jun expression, resulting in a depression of the AP1 transcription factor
complex and/or by a reduced nitric oxide production or an enhanced serotonergic activity.
The newly formed neurons are not able to overcome the schizophrenia-related loss of
parvalbumin expressing neurons and the behavioral abnormalities indicating that their
functional integration is crucial.
Key words
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Article info
Publication history
Published online: August 19, 2004
Accepted:
June 7,
2004
Received in revised form:
April 20,
2004
Received:
February 9,
2004
Identification
Copyright
© 2004 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
