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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 stimulates gene expression in hippocampus. (A) Immunohistochemistry for c-fos expression in hippocampal DG region after DMS with P5 treatment for 4 days. (B) Quantitation for c-fos positive cells in per 1 mm3. Values represent mean (±) SEM (n = 4 for each conditions; *: P < 0.05, student’s t-test). (C) mRNA level of fgf1b gene in hippocampus after DMS with P5 for 4 days. Values represent mean (±) SEM (n = 4 for each conditions; *: P < 0.05, student’s t-test). (D) Protein level of Fgf1b after DMS P5 treatment for 4 days. Hippocampal tissue samples were collected from control and animals received P5 daily treatment for 4 days. Samples were homogenized and analyzed by SDS-PAGE using antibodies indicated. (E) Quantification of (D).
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Figure 5: DMS stimulates gene expression in hippocampus. (A) Immunohistochemistry for c-fos expression in hippocampal DG region after DMS with P5 treatment for 4 days. (B) Quantitation for c-fos positive cells in per 1 mm3. Values represent mean (±) SEM (n = 4 for each conditions; *: P < 0.05, student’s t-test). (C) mRNA level of fgf1b gene in hippocampus after DMS with P5 for 4 days. Values represent mean (±) SEM (n = 4 for each conditions; *: P < 0.05, student’s t-test). (D) Protein level of Fgf1b after DMS P5 treatment for 4 days. Hippocampal tissue samples were collected from control and animals received P5 daily treatment for 4 days. Samples were homogenized and analyzed by SDS-PAGE using antibodies indicated. (E) Quantification of (D).

Mentions: To further explore the consequences at the molecular level caused by DMS treatment, we performed immunostaining and quantitative PCR to examine the change of gene expression in the hippocampus in vivo. Neural activity induces the modification of synaptic proteins, promotes local protein synthesis within dendrites and activates gene transcription in neurons. Therefore, we compared the expression level of several activity-dependent genes in the hippocampus between control groups and DMS-treated groups. The immediate early genes including c-fos, egr1 and arc are commonly used as markers for measuring neuronal activity in the brain. We first examined the expression of immediate early gene c-fos, in the DG after daily DMS with P5 paradigm for 4 days by immunohistochemistry. The results of immunostaining showed that the population of c-fos-positive neurons was significantly increased in DMS-treated animals (Figure 5A,B). Additionally, the Fgf1b gene is a brain-specific expressing gene encoding an important neurogenic niche factor in the adult hippocampus, and is induced by electroconvulsive stimulation [23]. We collected the hippocampal samples from animals with or without DMS treatment, further examined the mRNA levels of fgf1b in the DG by quantitative PCR. We found that the expression level of fgf1b was remarkably elevated after DMS (Figure 5C). Furthermore, we examined the protein level of Fgf1 in hippocampus with DMS treatment for 4 days. Consistently, we found that DMS treatment for 4 days significantly lead to an increase of protein level of Fgf1 in hippocampus (Figure 5D,E). These results suggest that DMS stimulation increases neural activity in the hippocampus, induces the expression of activity-dependent gene and leads to the release of neurogenic niche factors, which thereby promotes neurogenesis and plasticity in the adult brain.


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 stimulates gene expression in hippocampus. (A) Immunohistochemistry for c-fos expression in hippocampal DG region after DMS with P5 treatment for 4 days. (B) Quantitation for c-fos positive cells in per 1 mm3. Values represent mean (±) SEM (n = 4 for each conditions; *: P < 0.05, student’s t-test). (C) mRNA level of fgf1b gene in hippocampus after DMS with P5 for 4 days. Values represent mean (±) SEM (n = 4 for each conditions; *: P < 0.05, student’s t-test). (D) Protein level of Fgf1b after DMS P5 treatment for 4 days. Hippocampal tissue samples were collected from control and animals received P5 daily treatment for 4 days. Samples were homogenized and analyzed by SDS-PAGE using antibodies indicated. (E) Quantification of (D).
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3928113&req=5

Figure 5: DMS stimulates gene expression in hippocampus. (A) Immunohistochemistry for c-fos expression in hippocampal DG region after DMS with P5 treatment for 4 days. (B) Quantitation for c-fos positive cells in per 1 mm3. Values represent mean (±) SEM (n = 4 for each conditions; *: P < 0.05, student’s t-test). (C) mRNA level of fgf1b gene in hippocampus after DMS with P5 for 4 days. Values represent mean (±) SEM (n = 4 for each conditions; *: P < 0.05, student’s t-test). (D) Protein level of Fgf1b after DMS P5 treatment for 4 days. Hippocampal tissue samples were collected from control and animals received P5 daily treatment for 4 days. Samples were homogenized and analyzed by SDS-PAGE using antibodies indicated. (E) Quantification of (D).
Mentions: To further explore the consequences at the molecular level caused by DMS treatment, we performed immunostaining and quantitative PCR to examine the change of gene expression in the hippocampus in vivo. Neural activity induces the modification of synaptic proteins, promotes local protein synthesis within dendrites and activates gene transcription in neurons. Therefore, we compared the expression level of several activity-dependent genes in the hippocampus between control groups and DMS-treated groups. The immediate early genes including c-fos, egr1 and arc are commonly used as markers for measuring neuronal activity in the brain. We first examined the expression of immediate early gene c-fos, in the DG after daily DMS with P5 paradigm for 4 days by immunohistochemistry. The results of immunostaining showed that the population of c-fos-positive neurons was significantly increased in DMS-treated animals (Figure 5A,B). Additionally, the Fgf1b gene is a brain-specific expressing gene encoding an important neurogenic niche factor in the adult hippocampus, and is induced by electroconvulsive stimulation [23]. We collected the hippocampal samples from animals with or without DMS treatment, further examined the mRNA levels of fgf1b in the DG by quantitative PCR. We found that the expression level of fgf1b was remarkably elevated after DMS (Figure 5C). Furthermore, we examined the protein level of Fgf1 in hippocampus with DMS treatment for 4 days. Consistently, we found that DMS treatment for 4 days significantly lead to an increase of protein level of Fgf1 in hippocampus (Figure 5D,E). These results suggest that DMS stimulation increases neural activity in the hippocampus, induces the expression of activity-dependent gene and leads to the release of neurogenic niche factors, which thereby promotes neurogenesis and plasticity in the adult brain.

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