Transcriptional response to the neuroleptic-like compound Ampullosporin A in the rat ketamine model.
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.
Krügel
Hans
H
Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany. hans.kruegel@hki-jena.de
Becker
Axel
A
Polten
Andreas
A
Grecksch
Gisela
G
Singh
Ram
R
Berg
Albrecht
A
Seidenbecher
Constanze
C
Saluz
Hans-Peter
HP
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*
D014150:Antipsychotic Agents; D054848:Peptaibols; D010455:Peptides; D017981:Receptors, Neurotransmitter; C109004:ampullosporin; D007649:Ketamine; D002118:Calcium