Temporal gene expression profile after acute electroconvulsive stimulation in the rat
Mads Dyrvig1, Søren H Christiansen2, David P D Woldbye2
1Laboratory of Neurobiology, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
Abstract:
Electroconvulsive therapy (ECT) remains one of the most effective treatments of major depression. It has been suggested that the mechanisms of action involve gene expression. In recent decades there have been several investigations of gene expression following both acute and chronic electroconvulsive stimulation (ECS). These studies have focused on several distinct gene targets but have generally included only few time points after ECS for measuring gene expression. Here we measured gene expression of three types of genes: Immediate early genes, synaptic proteins, and neuropeptides at six time points following an acute ECS. We find significant increases for c-Fos, Egr1, Neuritin 1 (Nrn 1), Bdnf, Snap29, Synaptotagmin III (Syt 3), Synapsin I (Syn 1), and Psd95 at differing time points after ECS. For some genes these changes are prolonged whereas for others they are transient. Npy expression significantly increases whereas the gene expression of its receptors Npy1r, Npy2r, and Npy5r initially decreases. These decreases are followed by a significant increase for Npy2r, suggesting anticonvulsive adaptations following seizures. In summary, we find distinct changes in mRNA quantities that are characteristic for each gene. Considering the observed transitory and inverse changes in expression patterns, these data underline the importance of conducting measurements at several time points post-ECS.
Insights
Electroconvulsive stimulation (ECS) alters gene expression in the brain. This study reveals distinct, time-dependent changes in immediate early genes, synaptic proteins, and neuropeptides following ECS, highlighting the importance of multiple time point measurements.
Area of Science:
- Neuroscience
- Molecular Biology
- Psychiatry
Background:
- Electroconvulsive therapy (ECT) is a highly effective treatment for major depression.
- The underlying mechanisms of ECT are thought to involve alterations in gene expression.
- Previous studies on gene expression changes after electroconvulsive stimulation (ECS) have often used limited time points.
Purpose of the Study:
- To comprehensively investigate gene expression changes following acute ECS.
- To examine the temporal dynamics of immediate early genes, synaptic proteins, and neuropeptides.
- To understand the role of gene expression in the neurobiological effects of ECS.
Main Methods:
- Gene expression levels were measured at six distinct time points after a single ECS.
- Quantitative analysis focused on immediate early genes (e.g., c-Fos, Egr1), synaptic proteins (e.g., Bdnf, Snap29, Syt 3, Syn 1, Psd95), and neuropeptides (e.g., Npy and its receptors).
Main Results:
- Significant, time-dependent increases were observed for several genes including c-Fos, Egr1, Neuritin 1 (Nrn 1), Brain-Derived Neurotrophic Factor (Bdnf), Snap29, Synaptotagmin III (Syt 3), Synapsin I (Syn 1), and PSD-95.
- Changes in gene expression were either prolonged or transient, varying by gene.
- Neuropeptide Y (Npy) expression increased, while its receptors initially decreased before Npy2r showed a significant increase, suggesting adaptive responses.
Conclusions:
- Acute ECS induces characteristic and distinct changes in mRNA levels for various genes.
- The temporal patterns of gene expression, including transient and inverse changes, underscore the necessity of multi-time point analyses for a complete understanding of ECS effects.
- These findings contribute to elucidating the molecular mechanisms underlying the therapeutic effects of ECT.
