Transcriptional response to the neuroleptic‐like compound Ampullosporin A in the rat ketamine model
Hans Krügel, Axel Becker, Andreas Polten, Gisela Grecksch, Ram Singh, Albrecht Berg, Constanze Seidenbecher, Hans‐Peter Saluz
Journal of Neurochemistry April 1, 2006 DOI: 10.1111/j.1471-4159.2005.03621.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Ketamine-pretreated rats |
| Interventions | Ketamine Ampullosporin A |
| Dose | sub-anaesthetic doses of ketamine |
| Topics | Esketamine Ketamine |
| Key findings | In ketamine-pretreated rats, Ampullosporin A altered prefrontal cortex gene expression, with 63 genes up-regulated and 22 suppressed; transthyretin, syndecan-1 and NeuroD1 showed the highest up-regulation. The authors suggest Ampullosporin A may be a neuroleptic-like compound that induces changes in neurotransmitter receptor composition, calcium signalling and second messenger systems, and leads to plastic reorganization of brain tissue, metabolic pathways and synapses. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
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