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Comprehensive Analysis of Transcription Dynamics from Brain Samples Following Behavioral Experience
Published on: August 26, 2014
Behavioral sensitization to methamphetamine induces specific interneuronal mRNA pathology across the prelimbic and
Travis A Wearne1, Lindsay M Parker2, Jane L Franklin1
1Department of Psychology, Faculty of Human Sciences, Centre for Emotional Health, Macquarie University, Sydney, NSW, Australia.
Abstract:
Schizophrenia is associated with significant pathophysiological changes to interneurons within the prefrontal cortex (PFC), with mRNA and protein changes associated with the GABA network localized to specific interneuron subtypes. Methamphetamine is a commonly abused psychostimulant that can induce chronic psychosis and symptoms that are similar to schizophrenia, suggesting that chronic METH induced psychosis may be associated with similar brain pathology to schizophrenia in the PFC. The aim of this study, therefore, was to examine mRNA expression of interneuron markers across two regions of the PFC (prelimbic (PRL) and orbitofrontal cortices (OFC)) following METH sensitization, an animal model of METH psychosis. We also studied the association between GABA mRNA expression and interneuronal mRNA expression to identify whether particular changes to the GABA network could be localized to a specific inhibitory cellular phenotype. METH sensitization increased the transcriptional expression of calbindin, calretinin, somatostatin, cholecyctokinin and vasoactive intestinal peptide in the PRL while parvalbumin, calbindin, cholectokinin and vasoactive intestinal peptide were upregulated in the OFC. Based on our previous findings, we also found significant correlations between GAD67, GAT1 and parvalbumin while GAD67, GAD65 and GAT1 were positively correlated with cholecystokinin in the PRL of METH sensitized rats. Within the OFC, the expression of GABAAα1 was positively correlated with somatostatin while GABAAα5 was negatively associated with somatostatin and calbindin. These findings suggest that METH sensitization differentially changes the expression of mRNAs encoding for multiple peptides and calcium binding proteins across the PRL and the OFC. Furthermore, these findings support that changes to the GABA network may also occur within specific cell types. These results, therefore, provide the first evidence that METH sensitization mediates differential interneuronal pathology across the PRL and OFC and such changes could have profound consequences on behavior and cognitive output.
Insights
Methamphetamine (METH) sensitization alters gene expression in specific brain cells within the prefrontal cortex (PFC). These changes in interneurons suggest METH psychosis may share pathology with schizophrenia.
Area of Science:
- Neuroscience
- Psychiatry
- Molecular Biology
Background:
- Schizophrenia involves prefrontal cortex (PFC) interneuron dysfunction and GABA network alterations.
- Chronic methamphetamine (METH) psychosis shares symptoms with schizophrenia, suggesting similar neuropathology in the PFC.
Purpose of the Study:
- To investigate METH sensitization's effects on interneuron marker mRNA expression in the prelimbic (PRL) and orbitofrontal cortices (OFC) of the PFC.
- To determine if METH-induced GABA network changes are specific to interneuron subtypes.
Main Methods:
- Utilized METH sensitization as an animal model for METH psychosis.
- Analyzed mRNA expression of various interneuron markers (e.g., calbindin, parvalbumin) in the PRL and OFC.
- Examined correlations between GABA-related gene expression (e.g., GAD67) and interneuron markers.
Main Results:
- METH sensitization upregulated specific interneuron markers in the PRL (calbindin, calretinin, somatostatin, CCK, VIP) and OFC (parvalbumin, calbindin, CCK, VIP).
- Found significant correlations between GABAergic markers (GAD67, GAT1) and interneuron markers (parvalbumin, CCK) in the PRL.
- Observed associations between GABAA receptor subunits (GABAAα1, GABAAα5) and interneuron markers (somatostatin, calbindin) in the OFC.
Conclusions:
- METH sensitization induces distinct changes in interneuron gene expression across different PFC regions (PRL and OFC).
- These findings indicate that METH-induced alterations in the GABA network are localized to specific inhibitory cell types.
- Provides evidence for differential interneuronal pathology in the PRL and OFC due to METH sensitization, potentially impacting cognition.
