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Deep-brain magnetic stimulation promotes adult hippocampal neurogenesis and alleviates stress-related behaviors in mouse models for neuropsychiatric disorders.

Zhang Y, Mao RR, Chen ZF, Tian M, Tong DL, Gao ZR, Huang M, Li X, Xu X, Zhou WH, Li CY, Wang J, Xu L, Qiu Z - Mol Brain (2014)

Bottom Line: We found that DMS promotes adult hippocampal neurogenesis significantly and facilitates the development of adult new-born neurons.Remarkably, DMS exerts anti-depression effects in the learned helplessness mouse model and rescues hippocampal long-term plasticity impaired by restraint stress in rats.Moreover, DMS alleviates the stress response in a mouse model for Rett syndrome and prolongs the life span of these animals dramatically.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. lxu@vip.163.com.

ABSTRACT

Background: Repetitive Transcranial Magnetic Stimulation (rTMS)/ Deep-brain Magnetic Stimulation (DMS) is an effective therapy for various neuropsychiatric disorders including major depression disorder. The molecular and cellular mechanisms underlying the impacts of rTMS/DMS on the brain are not yet fully understood.

Results: Here we studied the effects of deep-brain magnetic stimulation to brain on the molecular and cellular level. We examined the adult hippocampal neurogenesis and hippocampal synaptic plasticity of rodent under stress conditions with deep-brain magnetic stimulation treatment. We found that DMS promotes adult hippocampal neurogenesis significantly and facilitates the development of adult new-born neurons. Remarkably, DMS exerts anti-depression effects in the learned helplessness mouse model and rescues hippocampal long-term plasticity impaired by restraint stress in rats. Moreover, DMS alleviates the stress response in a mouse model for Rett syndrome and prolongs the life span of these animals dramatically.

Conclusions: Deep-brain magnetic stimulation greatly facilitates adult hippocampal neurogenesis and maturation, also alleviates depression and stress-related responses in animal models.

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DMS facilitates development of DG new-born neurons. (A) Outline of DMS and retroviral-based new-born neuron label experiments. (B) GFP immunostaining with retroviral labeled new-born neurons after DMS treatment for 2 weeks. Green: GFP; Blue: DAPI staining. (C,D) Total dendritic length and tip numbers measured from (B) Values represent mean (±) SEM (n = 4 animals for each group; **: P < 0.005, ***: P < 0.0005, two-tailed student’s t-test). (E) Accumulative curve of dendritic length of neurons undergoing control, P1 and P5 treatment. (F) GFP immunostaining with retroviral labeled new-born neurons after DMS treatment for 4 weeks. Green: GFP; Blue: DAPI staining. (G,H) Total dendritic length and tip numbers measured from (F) Values represent mean (±) SEM (Animal amounts, control:n = 4, P5:n = 3; **: P < 0.005, *: P < 0.05, two-tailed student’s t-test). Scale bar = 25 μm.
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Figure 4: DMS facilitates development of DG new-born neurons. (A) Outline of DMS and retroviral-based new-born neuron label experiments. (B) GFP immunostaining with retroviral labeled new-born neurons after DMS treatment for 2 weeks. Green: GFP; Blue: DAPI staining. (C,D) Total dendritic length and tip numbers measured from (B) Values represent mean (±) SEM (n = 4 animals for each group; **: P < 0.005, ***: P < 0.0005, two-tailed student’s t-test). (E) Accumulative curve of dendritic length of neurons undergoing control, P1 and P5 treatment. (F) GFP immunostaining with retroviral labeled new-born neurons after DMS treatment for 4 weeks. Green: GFP; Blue: DAPI staining. (G,H) Total dendritic length and tip numbers measured from (F) Values represent mean (±) SEM (Animal amounts, control:n = 4, P5:n = 3; **: P < 0.005, *: P < 0.05, two-tailed student’s t-test). Scale bar = 25 μm.

Mentions: To address the effects of DMS on the maturation of new-born neurons, we labeled these neurons by stereotactic injection of retrovirus into the DG of young mice, followed by the 2-week daily treatment of DMS with distinct programs (Figure 4A) [22]. Retroviral infection of proliferating neural progenitor cells with the introduction of green fluorescent protein (GFP) allows the sparse labeling of new-born neurons and the elaborate observation of their morphological complexity. The morphology of GFP labeled new-born neurons was examined with confocal microscopy at 2 weeks post-injection (Figure 4B). The results showed that there was a significant increase in both the number of the tips and total dendritic length after DMS treatment with either P1 or P5, when compared to the control GFP labeled neurons (Figure 4C-E). We further applied DMS with Program 5 up to 4 weeks to mice which received retrovirus injection ahead of stimulation and analyzed the dendritic morphogenesis of new-born neurons (Figure 4F). Consistently, the results revealed that DMS robustly facilitated the dendritic growth and branching of neurons (Figure 4G-I).


Deep-brain magnetic stimulation promotes adult hippocampal neurogenesis and alleviates stress-related behaviors in mouse models for neuropsychiatric disorders.

Zhang Y, Mao RR, Chen ZF, Tian M, Tong DL, Gao ZR, Huang M, Li X, Xu X, Zhou WH, Li CY, Wang J, Xu L, Qiu Z - Mol Brain (2014)

DMS facilitates development of DG new-born neurons. (A) Outline of DMS and retroviral-based new-born neuron label experiments. (B) GFP immunostaining with retroviral labeled new-born neurons after DMS treatment for 2 weeks. Green: GFP; Blue: DAPI staining. (C,D) Total dendritic length and tip numbers measured from (B) Values represent mean (±) SEM (n = 4 animals for each group; **: P < 0.005, ***: P < 0.0005, two-tailed student’s t-test). (E) Accumulative curve of dendritic length of neurons undergoing control, P1 and P5 treatment. (F) GFP immunostaining with retroviral labeled new-born neurons after DMS treatment for 4 weeks. Green: GFP; Blue: DAPI staining. (G,H) Total dendritic length and tip numbers measured from (F) Values represent mean (±) SEM (Animal amounts, control:n = 4, P5:n = 3; **: P < 0.005, *: P < 0.05, two-tailed student’s t-test). Scale bar = 25 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 4: DMS facilitates development of DG new-born neurons. (A) Outline of DMS and retroviral-based new-born neuron label experiments. (B) GFP immunostaining with retroviral labeled new-born neurons after DMS treatment for 2 weeks. Green: GFP; Blue: DAPI staining. (C,D) Total dendritic length and tip numbers measured from (B) Values represent mean (±) SEM (n = 4 animals for each group; **: P < 0.005, ***: P < 0.0005, two-tailed student’s t-test). (E) Accumulative curve of dendritic length of neurons undergoing control, P1 and P5 treatment. (F) GFP immunostaining with retroviral labeled new-born neurons after DMS treatment for 4 weeks. Green: GFP; Blue: DAPI staining. (G,H) Total dendritic length and tip numbers measured from (F) Values represent mean (±) SEM (Animal amounts, control:n = 4, P5:n = 3; **: P < 0.005, *: P < 0.05, two-tailed student’s t-test). Scale bar = 25 μm.
Mentions: To address the effects of DMS on the maturation of new-born neurons, we labeled these neurons by stereotactic injection of retrovirus into the DG of young mice, followed by the 2-week daily treatment of DMS with distinct programs (Figure 4A) [22]. Retroviral infection of proliferating neural progenitor cells with the introduction of green fluorescent protein (GFP) allows the sparse labeling of new-born neurons and the elaborate observation of their morphological complexity. The morphology of GFP labeled new-born neurons was examined with confocal microscopy at 2 weeks post-injection (Figure 4B). The results showed that there was a significant increase in both the number of the tips and total dendritic length after DMS treatment with either P1 or P5, when compared to the control GFP labeled neurons (Figure 4C-E). We further applied DMS with Program 5 up to 4 weeks to mice which received retrovirus injection ahead of stimulation and analyzed the dendritic morphogenesis of new-born neurons (Figure 4F). Consistently, the results revealed that DMS robustly facilitated the dendritic growth and branching of neurons (Figure 4G-I).

Bottom Line: We found that DMS promotes adult hippocampal neurogenesis significantly and facilitates the development of adult new-born neurons.Remarkably, DMS exerts anti-depression effects in the learned helplessness mouse model and rescues hippocampal long-term plasticity impaired by restraint stress in rats.Moreover, DMS alleviates the stress response in a mouse model for Rett syndrome and prolongs the life span of these animals dramatically.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. lxu@vip.163.com.

ABSTRACT

Background: Repetitive Transcranial Magnetic Stimulation (rTMS)/ Deep-brain Magnetic Stimulation (DMS) is an effective therapy for various neuropsychiatric disorders including major depression disorder. The molecular and cellular mechanisms underlying the impacts of rTMS/DMS on the brain are not yet fully understood.

Results: Here we studied the effects of deep-brain magnetic stimulation to brain on the molecular and cellular level. We examined the adult hippocampal neurogenesis and hippocampal synaptic plasticity of rodent under stress conditions with deep-brain magnetic stimulation treatment. We found that DMS promotes adult hippocampal neurogenesis significantly and facilitates the development of adult new-born neurons. Remarkably, DMS exerts anti-depression effects in the learned helplessness mouse model and rescues hippocampal long-term plasticity impaired by restraint stress in rats. Moreover, DMS alleviates the stress response in a mouse model for Rett syndrome and prolongs the life span of these animals dramatically.

Conclusions: Deep-brain magnetic stimulation greatly facilitates adult hippocampal neurogenesis and maturation, also alleviates depression and stress-related responses in animal models.

Show MeSH
Related in: MedlinePlus