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Electroconvulsive Seizures in Rats and Fractionation of Their Hippocampi to Examine Seizure-induced Changes in Postsynaptic Density Proteins
Published on: August 15, 2017
Behavioral and molecular responses to electroconvulsive shock differ between genetic and environmental rat models of
1Department of Anesthesiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Abstract:
Depression׳s causes play a role in individuals׳ different responses to antidepressant treatments, which require advancements. We investigated the mechanisms behind and responses to a highly effective antidepressant treatment, electroconvulsive therapy (ECT), in rat models with different (genetic or environmental) depression causes. Wistar Kyoto (WKY) rats and Wistar rats treated with chronic unpredictable mild stresses (CUMS) were used as genetic and environmental rat models of depression, respectively. The rats underwent electroconvulsive shock (ECS, the animal analog of ECT) or sham ECS. We performed a sucrose preference test, open field test, and Morris water maze to assess behavior. Hippocampal neuron numbers were measured with Nissl stain. Hippocampal BDNF, CREB, and p-CREB proteins were assayed with ELISA or western blotting. The main results showed that ECS impaired WKY rats׳ memories but improved CUMS rats׳ memories. It elevated hippocampal BDNF and CREB proteins only in CUMS rats, while it improved depressive behavior and hippocampal p-CREB protein levels in both rats, with more effective regulations in the CUMS rats. ECS did not change the hippocampal neuron number in both rats. These findings suggest that ECS exerted up-regulating effects on hippocampal BDNF and CREB (and its phosphorylation) in depressed rats, and the environmental model responded better.
Insights
Electroconvulsive shock (ECS) improved depression in rat models. Environmental stress models showed better memory and molecular responses to ECS compared to genetic models.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- Depression treatment response varies due to underlying causes.
- Advancements in understanding antidepressant mechanisms are needed.
- Electroconvulsive therapy (ECT) is an effective antidepressant treatment.
Purpose of the Study:
- Investigate electroconvulsive shock (ECS) mechanisms and responses in distinct depression models.
- Compare ECS efficacy in genetic (Wistar Kyoto rats) versus environmental (CUMS-exposed Wistar rats) depression models.
Main Methods:
- Utilized Wistar Kyoto (WKY) and chronic unpredictable mild stress (CUMS) rat models.
- Administered electroconvulsive shock (ECS) or sham ECS.
- Assessed behavior via sucrose preference, open field, and Morris water maze tests.
- Measured hippocampal neuron counts (Nissl stain) and protein levels (BDNF, CREB, p-CREB via ELISA/Western blot).
Main Results:
- ECS improved depressive behavior and hippocampal p-CREB in both rat models.
- ECS enhanced memory in CUMS rats but impaired it in WKY rats.
- Hippocampal BDNF and CREB levels increased only in CUMS rats following ECS.
- No significant changes in hippocampal neuron numbers were observed.
Conclusions:
- ECS up-regulates hippocampal BDNF, CREB, and phosphorylation in depressed rats.
- Environmental depression models demonstrate a superior response to ECS compared to genetic models.
- Differential responses highlight the influence of depression etiology on treatment efficacy.
