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

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

doi:10.1016/S0165-3806(02)00639-9

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

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

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

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 language	English (US)
Pages (from-to)	33-37
Number of pages	5
Journal	Developmental Brain Research
Volume	141
Issue number	1-2
DOIs	https://doi.org/10.1016/S0165-3806(02)00639-9
State	Published - Mar 14 2003
Externally published	Yes

Keywords

Animal model
GSK-3
Neurodevelopment
Schizophrenia

ASJC Scopus subject areas

Developmental Neuroscience
Developmental Biology

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10.1016/S0165-3806(02)00639-9

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

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.",

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author = "Carmit Nadri and Lipska, {Barbara K.} and Nitsan Kozlovsky and Weinberger, {Daniel R.} and Belmaker, {Robert H.} and Galila Agam",

note = "Funding Information: This study was supported by a NARSAD young investigator award to N.K.",

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AU - Nadri, Carmit

AU - Lipska, Barbara K.

AU - Kozlovsky, Nitsan

AU - Weinberger, Daniel R.

AU - Belmaker, Robert H.

AU - Agam, Galila

N1 - Funding Information: This study was supported by a NARSAD young investigator award to N.K.

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N2 - 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.

AB - 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.

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

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