Glycogen synthase kinase (GSK)-3β levels and activity in a neurodevelopmental rat model of schizophrenia

Carmit Nadri, Barbara K. Lipska, Nitsan Kozlovsky, Daniel Weinberger, Robert H. Belmaker, Galila Agam

Research output: Contribution to journalArticle

Abstract

We have previously reported reduced GSK-3β protein levels and GSK-3 total (α+β isoforms) activity in postmortem frontal cortex of schizophrenic patients. We now studied whether GSK-3β is altered in the frontal cortex of rats with the neonatal excitotoxic hippocampal lesion used as a model of schizophrenia. Rats were infused with ibotenic acid (or artificial CSF in controls) bilaterally into the ventral hippocampus (VH) at postnatal day 7, then killed at postnatal day 35 (pre-puberty) or 56 (post-puberty). GSK-3β protein levels were reduced in the frontal cortex of the lesioned rats as compared to sham animals; post-hoc comparisons revealed that the reduction was statistically significant at a pre-pubertal age. Total GSK-3 (α+β) activity was not different between lesioned and sham rats at any age. These results demonstrate that reduced frontal cortical GSK-3β levels may occur as a result of neonatal hippocampal damage and suggest that this animal model may be utilized to study the mechanism of GSK-3 reduction in schizophrenia, a disorder in which postmortem changes in GSK-3 were found.

Original languageEnglish (US)
Pages (from-to)33-37
Number of pages5
JournalDevelopmental Brain Research
Volume141
Issue number1-2
DOIs
StatePublished - Mar 14 2003
Externally publishedYes

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Glycogen Synthase Kinase 3
Schizophrenia
Frontal Lobe
Postmortem Changes
Ibotenic Acid
Puberty
Hippocampus
Protein Isoforms
Proteins
Animal Models

Keywords

  • Animal model
  • GSK-3
  • Neurodevelopment
  • Schizophrenia

ASJC Scopus subject areas

  • Developmental Biology
  • Developmental Neuroscience

Cite this

Glycogen synthase kinase (GSK)-3β levels and activity in a neurodevelopmental rat model of schizophrenia. / Nadri, Carmit; Lipska, Barbara K.; Kozlovsky, Nitsan; Weinberger, Daniel; Belmaker, Robert H.; Agam, Galila.

In: Developmental Brain Research, Vol. 141, No. 1-2, 14.03.2003, p. 33-37.

Research output: Contribution to journalArticle

Nadri, Carmit ; Lipska, Barbara K. ; Kozlovsky, Nitsan ; Weinberger, Daniel ; Belmaker, Robert H. ; Agam, Galila. / Glycogen synthase kinase (GSK)-3β levels and activity in a neurodevelopmental rat model of schizophrenia. In: Developmental Brain Research. 2003 ; Vol. 141, No. 1-2. pp. 33-37.
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