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1 Acta Neurobiologiae Experimentalis

1 2009

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Brain level of FKBP-51, a glucocorticoid receptor cochaperone, is decreased in a neurodevelopmental animal model of schzophrenia

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Basta-Kaim A. , Budziszewska B. , Kabera M. , Leskiewicz M. , Regulska M. , Korzeniak B.

Acta Neurobiologiae Experimentalis

2009

tom 69

nr 3

Recent studies suggest that dysregulation of the HPA axis activity and disturbance in glucocorticoid receptor (GR) action are involved in the pathogenesis of schizophrenia. The hyperfunction of GR can result from alterations in GR phosphorylation status or numbers of its cochaperones. The most important GR cochaperone FKBP-51, is known to inhibit GR transcriptional activity. The aim of the present work was to investigate the concentration of the immunophilin FKBP-51 in the hippocampus and frontal cortex in a neurodevelopmental animal model of schizophrenia. This model is based on administration of lipopolysaccharide to pregnant rats (in the second and third week of pregnancy). Amount of FKBP-51 was measured by Western blot method. In order to verify the above model, exploration, effi cacy of sensorimotor gating and performance in the social interaction test were determined. Prenatal LPS treatment induced behavioral disturbances typical of schizophrenia, like sensorimotor gating defi cit, higher exploratory activity and changes in social interaction test in the adult offspring. Furthermore, the level of the immunophilin FKBP51 was lower in both female and male offspring. These results suggest that multiple administrations of LPS to pregnant rats evoke GR hyperfunction in adult offspring by decreasing the concentration of FKBP-51, a protein which is known to inhibit GR function. This study was partially supported by the grant N40101231/0174 from the MSHE, Warsaw, Poland.