Differential regulation of chromogranin A, chromogranin B and secretogranin II in rat brain by phencyclidine treatment

Chromogranin A, chromogranin B and secretogranin II belong to the chromogra nin family which consists of large protein molecules that are found in larg e dense core vesicles. Chromogranins are endoproteolytically processed to s maller peptides. This study was designed to elucidate the regulation of chromgranin expressi on by acute and subchronic phencyclidine administration. The behavioral syn drome produced by phencyclidine represents a pharmacological model for some aspects of schizophrenia [Jentsch and Roth (1999) Neuropsychopharmacology 20, 201-225]. Tissue concentrations of chromogranins were measured with spe cific radioimmunoassays. Alterations in secretogranin II gene expression we re investigated by in situ hybridization. A single dose of phencyclidine (1 0 mg/kg) led to a transient decrease in secretoneurin tissue levels in the prefrontal cortex after 4 h followed by an increase in secretoneurin tissue levels after 12 h. Repeated phencyclidine treatment (10 mg/kg/day) for fiv e days resulted in elevated secretoneurin levels in cortical areas whereas chromogranin A and chromogranin B tissue levels were unchanged. After the s ame treatment a significant increase in the number of secretoneurin contain ing neurons was found in cortical layers II-III, and V-VI as revealed by im munocytochemistry. The increases in secretoneurin levels were paralleled by an increased number of secretogranin II messenger RNA containing neurons a s well as by an increased expression of secretogranin II by individual neur ons. The present study shows that secretoneurin II tissue concentration and secr etogranin II messenger RNA expression is distinctly altered after acute and subchronic phencyclidine application. From these results we suggest that p hencyclidine may induce synaptic alterations in specific brain areas and ma y contribute to a better understanding of synaptic dysfunction which may al so occur in schizophrenia. (C) 2001 IBRO. Published by Elsevier Science Ltd . All rights reserved.