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Transcriptional response to the neuroleptic‐like compound Ampullosporin A in the rat ketamine model
Author(s) -
Krügel Hans,
Becker Axel,
Polten Andreas,
Grecksch Gisela,
Singh Ram,
Berg Albrecht,
Seidenbecher Constanze,
Saluz HansPeter
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03621.x
Subject(s) - ketamine , neuroscience , schizophrenia (object oriented programming) , pharmacology , psychology , medicine , psychiatry
Abstract Psychotic disorders affecting up to 1% of the human population represent pathological changes to the metabolic homeostasis of the brain. Increasing evidence in the literature suggests complex biochemical and/or transcriptional alterations accompanying schizophrenia‐like phenomena. Sub‐chronic treatment with sub‐anaesthetic doses of ketamine induces schizophrenia‐related psychotic alterations that can be used as an animal model in the study of this disorder. Ampullosporin A belongs to a specific group of pore‐forming fungal peptides, peptaibols. We focused on the analysis of molecular events occurring in the brain of ketamine‐pre‐treated rats after administration of Ampullosporin A with neuroleptic‐like activity. The complex experimental approach allowed us to correlate the use of low molecular weight substances with a transcriptome fingerprint in the prefrontal cortex. We found 63 genes to be up‐regulated and 22 genes suppressed, with transthyretin, syndecan‐1 and NeuroD1 showing the highest degree of up‐regulation. Our results suggest the possibility that Ampullosporin A belongs to the group of neuroleptic‐like compounds, inducing massive changes in neurotransmitter receptor composition, calcium signalling cascades and second messenger systems, and leading to the plastic reorganization of brain tissue, metabolic pathways and synapses.