title: Transcriptional response to the neuroleptic-like compound Ampullosporin A in the rat ketamine model.
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.
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany. hans.kruegel@hki-jena.de
authors.forename: Hans
authors.initials: H
authors.lastname: Krügel
authors.forename: Axel
authors.initials: A
authors.lastname: Becker
authors.forename: Andreas
authors.initials: A
authors.lastname: Polten
authors.forename: Gisela
authors.initials: G
authors.lastname: Grecksch
authors.forename: Ram
authors.initials: R
authors.lastname: Singh
authors.forename: Albrecht
authors.initials: A
authors.lastname: Berg
authors.forename: Constanze
authors.initials: C
authors.lastname: Seidenbecher
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Saluz
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D007649:Ketamine; D020411:Oligonucleotide Array Sequence Analysis; D054848:Peptaibols; D010455:Peptides / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D012559:Schizophrenia / Q000139:chemically induced / Q000378:metabolism*; D015290:Second Messenger Systems / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D054848:Peptaibols; D010455:Peptides; D017981:Receptors, Neurotransmitter; C109004:ampullosporin; D007649:Ketamine; D002118:Calcium