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A marked effect of electroconvulsive stimulation on behavioral aberration of mice with neuron-specific mitochondrial DNA defects.

Kasahara T, Kubota M, Miyauchi T, Ishiwata M, Kato T - PLoS ONE (2008)

Bottom Line: Electroconvulsive therapy, which has long been used in clinical practice, provides fast-acting relief to depressive patients and drug-resistant patients.To study the mechanism of the action, we investigated whether ECS could alter the circadian phase but found no influence on the circadian clock system.This model will be useful in developing a safe and effective alternative to lithium or electroconvulsive therapy.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Molecular Dynamics of Mental Disorders, Brain Science Institute, RIKEN, Wako-shi, Saitama, Japan. casa@brain.riken.jp

ABSTRACT
We developed transgenic (Tg) mice modeling an autosomally inherited mitochondrial disease, chronic progressive external ophthalmoplegia, patients with which sometimes have comorbid mood disorders. The mutant animals exhibited bipolar disorder-like phenotypes, such as a distorted day-night rhythm and a robust activity change with a period of 4-5 days, and the behavioral abnormalities were improved by lithium. In this study, we tested the effect of electroconvulsive stimulation (ECS) on the behavioral abnormalities of the model. Electroconvulsive therapy, which has long been used in clinical practice, provides fast-acting relief to depressive patients and drug-resistant patients. We performed long-term recordings of wheel-running activity of Tg and non-Tg mice. While recording, we administrated a train of ECS to mice, six times over two weeks or three times over a week. The treatment ameliorated the distorted day-night rhythm within three times of ECS, but it had no effect on the activity change with a period of 4-5 days in the female mice. To study the mechanism of the action, we investigated whether ECS could alter the circadian phase but found no influence on the circadian clock system. The potent and fast-acting efficacy of ECS in the mutant mice supports the predictive validity of the mice as a model of bipolar disorder. This model will be useful in developing a safe and effective alternative to lithium or electroconvulsive therapy.

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Related in: MedlinePlus

Wheel-running activity records of representative mice receiving ECS.Mice were delivered ECS (red triangles) six times (A) or three times (B). The light and dark periods (12:12 h) are indicated by white and gray backgrounds, respectively.
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pone-0001877-g001: Wheel-running activity records of representative mice receiving ECS.Mice were delivered ECS (red triangles) six times (A) or three times (B). The light and dark periods (12:12 h) are indicated by white and gray backgrounds, respectively.

Mentions: We delivered ECS six times over 2 weeks in the first experiment (Fig. 1A); this treatment schedule conformed to the standard ECT regime for patients with mood disorder. ECS seemed to improve the distorted day–night rhythm of the mutPOLG Tg mice; however, more than half of the treated mice died after ECS probably due to respiratory failure, and it became impossible to statistically analyze the effect of ECS. Therefore, in the second experiment, mice breathed in oxygen gas for about 1 min before receiving the electroshock. Oxygenation was highly effective, and mice rarely died after ECS.


A marked effect of electroconvulsive stimulation on behavioral aberration of mice with neuron-specific mitochondrial DNA defects.

Kasahara T, Kubota M, Miyauchi T, Ishiwata M, Kato T - PLoS ONE (2008)

Wheel-running activity records of representative mice receiving ECS.Mice were delivered ECS (red triangles) six times (A) or three times (B). The light and dark periods (12:12 h) are indicated by white and gray backgrounds, respectively.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2267493&req=5

pone-0001877-g001: Wheel-running activity records of representative mice receiving ECS.Mice were delivered ECS (red triangles) six times (A) or three times (B). The light and dark periods (12:12 h) are indicated by white and gray backgrounds, respectively.
Mentions: We delivered ECS six times over 2 weeks in the first experiment (Fig. 1A); this treatment schedule conformed to the standard ECT regime for patients with mood disorder. ECS seemed to improve the distorted day–night rhythm of the mutPOLG Tg mice; however, more than half of the treated mice died after ECS probably due to respiratory failure, and it became impossible to statistically analyze the effect of ECS. Therefore, in the second experiment, mice breathed in oxygen gas for about 1 min before receiving the electroshock. Oxygenation was highly effective, and mice rarely died after ECS.

Bottom Line: Electroconvulsive therapy, which has long been used in clinical practice, provides fast-acting relief to depressive patients and drug-resistant patients.To study the mechanism of the action, we investigated whether ECS could alter the circadian phase but found no influence on the circadian clock system.This model will be useful in developing a safe and effective alternative to lithium or electroconvulsive therapy.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Molecular Dynamics of Mental Disorders, Brain Science Institute, RIKEN, Wako-shi, Saitama, Japan. casa@brain.riken.jp

ABSTRACT
We developed transgenic (Tg) mice modeling an autosomally inherited mitochondrial disease, chronic progressive external ophthalmoplegia, patients with which sometimes have comorbid mood disorders. The mutant animals exhibited bipolar disorder-like phenotypes, such as a distorted day-night rhythm and a robust activity change with a period of 4-5 days, and the behavioral abnormalities were improved by lithium. In this study, we tested the effect of electroconvulsive stimulation (ECS) on the behavioral abnormalities of the model. Electroconvulsive therapy, which has long been used in clinical practice, provides fast-acting relief to depressive patients and drug-resistant patients. We performed long-term recordings of wheel-running activity of Tg and non-Tg mice. While recording, we administrated a train of ECS to mice, six times over two weeks or three times over a week. The treatment ameliorated the distorted day-night rhythm within three times of ECS, but it had no effect on the activity change with a period of 4-5 days in the female mice. To study the mechanism of the action, we investigated whether ECS could alter the circadian phase but found no influence on the circadian clock system. The potent and fast-acting efficacy of ECS in the mutant mice supports the predictive validity of the mice as a model of bipolar disorder. This model will be useful in developing a safe and effective alternative to lithium or electroconvulsive therapy.

Show MeSH
Related in: MedlinePlus