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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

No influence of ECS on the circadian clock.Double-plotted activity records of representative mice receiving one ECS (red triangles) at different times of the day: circadian time (CT) 0, 4, 8, 12, 16, and 20. CT0–12 is the subjective light phase, and CT12–24 is the subjective dark phase. The light and dark periods are indicated by white and gray backgrounds, respectively. Onset of activity shown by green lines was used as the reference phase for the determination of phase shift.
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pone-0001877-g003: No influence of ECS on the circadian clock.Double-plotted activity records of representative mice receiving one ECS (red triangles) at different times of the day: circadian time (CT) 0, 4, 8, 12, 16, and 20. CT0–12 is the subjective light phase, and CT12–24 is the subjective dark phase. The light and dark periods are indicated by white and gray backgrounds, respectively. Onset of activity shown by green lines was used as the reference phase for the determination of phase shift.

Mentions: In some cases, ECS-treated mice showed regular day–night rhythm soon after the first ESC. The immediate effect of ECS allowed us to assume that ECS induced phase shifts of the circadian clock and adjusted the day–night rhythm. ECS as well as transcranial magnetic stimulation induced c-fos mRNA expression in the suprachiasmatic nucleus (SCN) [12], where the master circadian clock located. It is also known that c-fos expression is coincident with light-induced phase-shift of the circadian clock [13], [14]. Thus, it might be possible that ECS improved the phenotype of the mice by directly affecting the SCN. To test this hypothesis, we examined whether ECS could alter the phase of circadian clock system. Animals were transferred and maintained in constant darkness, resulting in the free-running of circadian clock. Then we delivered a single ECS under dim red light at various times of day. We observed no phase shift caused by the ECS at any time of the day (Fig. 3).


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)

No influence of ECS on the circadian clock.Double-plotted activity records of representative mice receiving one ECS (red triangles) at different times of the day: circadian time (CT) 0, 4, 8, 12, 16, and 20. CT0–12 is the subjective light phase, and CT12–24 is the subjective dark phase. The light and dark periods are indicated by white and gray backgrounds, respectively. Onset of activity shown by green lines was used as the reference phase for the determination of phase shift.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0001877-g003: No influence of ECS on the circadian clock.Double-plotted activity records of representative mice receiving one ECS (red triangles) at different times of the day: circadian time (CT) 0, 4, 8, 12, 16, and 20. CT0–12 is the subjective light phase, and CT12–24 is the subjective dark phase. The light and dark periods are indicated by white and gray backgrounds, respectively. Onset of activity shown by green lines was used as the reference phase for the determination of phase shift.
Mentions: In some cases, ECS-treated mice showed regular day–night rhythm soon after the first ESC. The immediate effect of ECS allowed us to assume that ECS induced phase shifts of the circadian clock and adjusted the day–night rhythm. ECS as well as transcranial magnetic stimulation induced c-fos mRNA expression in the suprachiasmatic nucleus (SCN) [12], where the master circadian clock located. It is also known that c-fos expression is coincident with light-induced phase-shift of the circadian clock [13], [14]. Thus, it might be possible that ECS improved the phenotype of the mice by directly affecting the SCN. To test this hypothesis, we examined whether ECS could alter the phase of circadian clock system. Animals were transferred and maintained in constant darkness, resulting in the free-running of circadian clock. Then we delivered a single ECS under dim red light at various times of day. We observed no phase shift caused by the ECS at any time of the day (Fig. 3).

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