Repetitive magnetic stimulation promotes the proliferation of neural progenitor cells via modulating the expression of miR-106b

  • Authors:
    • Hua Liu
    • Gaohua Li
    • Chunlian Ma
    • Yanfang Chen
    • Jinju Wang
    • Yi Yang
  • View Affiliations

  • Published online on: October 9, 2018     https://doi.org/10.3892/ijmm.2018.3922
  • Pages: 3631-3639
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Abstract

Increasing evidence shows that repetitive transcranial magnetic stimulation (rTMS) promotes neurogenesis and the expression of microRNA (miR)‑106b. The present study investigated whether rTMS promotes the proliferation of neural progenitor cells (NPCs) and whether the effect is associated with the expression of miR‑106b. NPCs were cultured from the rat hippocampus and exposed to rTMS daily, comprising 1,000 stimuli for 3 days at 10 Hz, with 1.75 T output. The proliferation ability of the NPCs was revealed by EdU staining, and the levels of miR‑106b and downstream gene p21 in the NPCs were measured by reverse transcription‑quantitative polymerase chain reaction and western blot analyses. For analysis of the mechanism, the NPCs were transfected with Lenti‑miR‑106b or small interfering RNAs prior to rTMS. The results showed that: i) rTMS increased NPC proliferation, as revealed by the increased proportion of EdU‑positive cells; ii) rTMS was able to upregulate the expression of miR‑106b and downregulate the level of p21 in NPCs; iii) overexpression of miR‑106b further enhanced the effects of rTMS, whereas knockdown of miR‑106b had the opposite effects. Taken together, these data indicated that rTMS can promote NPC proliferation by upregulating the expression of miR‑106b and possibly inhibiting the expression of p21.

Introduction

Repetitive transcranial magnetic stimulation (rTMS), as a non-invasive stimulation technique delivering a repetitive pulsed magnetic field, has been widely applied in treating various neurological diseases, including depression (1), pain (2), epilepsy (3), headache (4), insomnia (5) and Alzheimer's disease (6). Although the relevant mechanisms remain to be elucidated, rTMS treatment can induce neural plasticity effects, as evidenced by functional magnetic resonance imaging (fMRI) (7) and positron emission tomography (PET) analyses (8). In addition, rTMS has been demonstrated to influence glucose metabolism (8), long-term potentiation (9), the activity of ion channels (10), and the expression of plasticity-associated genes (11).

Neural progenitor cells (NPCs) in the subgranular zone (SGZ) and subventricular zone (SVZ) of the brain can self-renew, proliferate, migrate and differentiate (12). Following cerebral ischemia, NPCs are activated for proliferation and can migrate to the injured region for neuron repair and regeneration (13). rTMS has been shown to increase NPC proliferation in the SGZ of healthy rats (14) and in the SVZ of focal cerebral ischemia rats (15). However, the underlying mechanism of rTMS remains to be fully elucidated.

MicroRNAs (miRs) are 20-40-bp small non-coding RNAs, which can inhibit the translation of mRNAs involved in various physiological and pathological processes (16). Increasing evidence indicates that miRs modulate the proliferation of NPCs (17,18). Using array analysis, a previous study identified that miR-106b may promote the proliferation of NPCs (17). Brett et al (19) demonstrated that overexpressing the entire miR106b~25 cluster enhanced the proliferation of in vitro cultured NPCs. According to the analysis of targeting gene prediction (www.targetscan.org, and Kyoto Encyclopedia of Genes and Genomes), p21 of the cyclin-dependent kinase inhibitor (CDKI) family is negatively regulated by miR-106b, which has been shown to contribute to cell proliferation through accelerating the G1-to-S transition (20,21). In addition, the expression of p21 can be regulated by other miRs (22,23) in other types of cells. However, whether miR-106b can modulate the expression of p21 in NPCs has not been investigated.

Our previous study (24) indicated that rTMS was able to directly induce the proliferation of NPCs accompanied with the upregulation of miR-106b. The present study aimed to further investigate the effects of rTMS on cultured NPCs transfected with Lenti-miR-106b or small interfering (si)RNAs to clarify whether rTMS promotes NPC proliferation by upregulating the expression of miR-106b and possibly inhibiting the expression of p21.

Materials and methods

Reagents

The primary antibodies and reagents used were as follows: Dulbecco's modified Eagle's medium/Nutrient Mixture F-12 (DMEM/F12; Gibco; Thermo Fisher Scientific, Inc., Waltham, MA, USA), B-27® Supplement (Invitrogen; Thermo Fisher Scientific, Inc.), basic fibroblast growth factor (b-FGF; Peprotech, Inc., Rocky Hill, NJ, USA), epidermal growth factor (EGF; Peprotech, Inc.), TrypLE™ Express Enzyme (Gibco; Thermo Fisher Scientific, Inc.), poly-L-lysine (Sigma; Merck KGaA, Darmstadt, Germany), β-actin antibody (cat. no. BM0627; Wuhan Boster Biological Technology Co., Ltd., Wuhan, China), EdU (Ruibo Biological Technology Co., Ltd., Guangzhou, China), mouse anti-rat nestin (cat. no. 556309; BD Biosciences, Franklin Lakes, NJ, USA), FITC-labeled rabbit anti-mouse IgG (cat. no. 315-005-003; Jackson ImmunoResearch Laboratories, Inc., West Grove, PA, USA).

Preparation of proliferation medium

For the production of 100 ml of proliferation medium, 98 ml DMEM/F12 medium, 2 ml B-27® without vitamin A, 2 µg b-FGF and 2 µg EGF were mixed, sterilized using a 0.22-µm filter in a laminar flow hood, and stored in a 4°C refrigerator.

Culture of NPC neurospheres

The NPC neurospheres were cultured as previously described (25). In brief, bilateral hippocampal tissues were rapidly dissected from the brains of 10-15 neonatal Sprague-Dawley rats within 3 days of birth for each experiment. The neonatal rats (weight, 5-6 g) were provided by Tongji Medical College Experimental Animal Center of Huazhong Technology University (Huazhong, China). Rooms were maintained at 20-24°C (50% relative humidity) and a 12-h light/dark cycle. The hippocampal tissues were placed into cold Hank's Buffered Salt Solution (HBSS; Sigma-Aldrich; Merck KGaA), Following enzyme digestion with TrypLE™ Express (Gibco; Thermo Fisher Scientific, Inc.) in a 5% CO2 incubator (37°C for 2 min), the tissues were mechanically dissociated using a pipette several times, and centrifuged (300 x g 5 min, 4°C). The cells were suspended in the proliferation medium, as described above, and were seeded (104-5 cells/ml, passage one) in dishes for culture with DMEM/F12 in a 5% CO2 incubator at 37°C. The neurospheres were subcultured every 5 days. The second generation of NPCs was prepared for rTMS. All experimental procedures were approved by the ethics committee of the Wuhan Sports University (Wuhan, China).

Experimental design

The experimental design is outlined in Fig. 1A. The NPCs were used for rTMS and miR overexpression/downregulation experiments. For the over-expression of miR-106b, the NPCs were transfected with lentivirus (Lenti)-null, or Lenti-miR-106b for 48 h prior to rTMS. For the downregulation of miR-106b, the NPCs were transfected with miR-106b siRNA using Lipofectamine™ 2000 (Invitrogen; Thermo Fisher Scientific, Inc.) for 6 h prior to rTMS. Following 3 days of stimulation, the NPCs were used for EdU staining or miR/protein analyses. In the sham group, the NPCs were treated with rTMS without stimuli output. An empty lentivirus or Lipofectamine 2000 without siRNA was used for the respective negative control groups (Lenti-null + sham: LN; negative control + sham: NC). The groups were named as follows: Lenti-miR-106b + sham: L106b; Lenti-miR-106b + rTMS: L106bS; anti-miR-106b + sham: A106b; anti-miR-106b + rTMS: A106bS.

Transfection of the NPCs with Lenti-miR-106b or miR-106b siRNA

The pLVX-ZsGreen-Puro-rno-miR-106b vector (Wuhan Biofavor Co., Ltd., Wuhan, China) was transfected into 293T cells (Wuhan Biofavor Co., Ltd.) to generate high-titer lentivirus (biological titer, 1.0x108 TU/ml) containing miR-106b. The NPCs were infected with the lentivirus based on the equation that MOI=30. The cells were re-suspended in 2 ml of complete medium, and incubated with 1.5x107 TU lentivirus at 37°C with 5% CO2 for 48 h. Subsequently, the medium containing the NPCs was replaced with fresh medium to obtain 80% confluence. The siRNAs for miR-106b-5p (5'-UAA AGU GCU GAC AGU GCA GAU-3') were synthesized by GenePharma Co., Ltd. (Shanghai, China). The NPCs were re-suspended at 105 cells/ml in Opti-MEM medium (Invitrogen; Thermo Fisher Scientific, Inc.), and transferred into flasks to culture for 2 h. According to the manufacturer's protocol, the miR-106b siRNAs were transiently transfected into NPCs using siRNA-Lipofectamine 2000 (Invitrogen; Thermo Fisher Scientific, Inc.) and cultured for 48 h at 37°C with 5% CO2. The NPCs were then treated with rTMS.

rTMS

The NPCs with or without miR modification were treated by sham or rTMS using a CCy-I type transcranial magnetic stimulation instrument (Wuhan Yiruide Medical Equipment Co., Ltd., Wuhan, China) according to a previous study (24). In brief, the culture dish was placed in the cross-center of an ‘8’-shaped magnetic coil which had a stimulus distance of rTMS of <1 cm between the cells and the coil (Fig. 1B). The rTMS was performed daily at 1,000 stimuli for 3 days at 10 Hz, with 1.75 T output. The neurospheres were examined under a light microscope (Fig. 1C).

Immunofluroscence and EdU staining

Following 3 days of rTMS, the cells were stained with nestin, which is a common marker of NPCs. The resuspended neurospheres were seeded into the 24-well glass slides coated with polylysine, and fixed with -20°C methanol for 20 min. Subsequently, for the immunostaining of nestin, each coverslip was incubated with 20 µl mouse anti-rat nestin antibody (1:100) at 4°C overnight. The cells were then incubated with secondary FITC-labeled rabbit anti-mouse IgG (1:400) for 2 h at room temperature, protected from the light. DAPI was added for nuclear staining for 15 min at room temperature.

EdU staining was used to determine the proliferative NPCs. The re-suspended NPCs in each 24-well contained 500 µl solution which was diluted with the culture medium at a ratio of 1,000:1 (reagent A) and cultured for 2 h. The medium was the discarded and 500 µl of pre-cooling pure methanol was added for fixation at room temperature for 20 min. The slides were then stained with 1X Apollo® staining reaction solution and 1X Hoechst 33342 reaction solution for 30 min respectively at room temperature (Fig. 1D).

Immunofluorescence images were observed using the Olympus Bx51 fluorescence microscope. A total of five randomly-selected fields were counted in a blinded-manner using image processing software (ImageJ, v.1.6.0; National Institutes of Health, Bethesda, MD, USA) for quantification.

Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis

According to the manufacturer's protocol, the total RNA of the cells was isolated using TRIzol reagent (Thermo Fisher Scientific, Inc.) and RNA concentration was measured using a spectrophotometer. The reverse transcription of RNA was performed using a TaqMan MicroRNA Reverse Transcription kit (Applied Biosystems; Thermo Fisher Scientific, Inc.) at 70°C for 5 min, 42°C for 60 min, and 95°C for 5 min. To quantify the expression of miR-106b, a 20-µl reaction system included 100 µM/l rno-miR-106b forward and rno-miR-106b reverse primer, 10 µl SYBR Green/Flourescein qPCR Master mix (2X; Takara Bio, Inc., Otsu, Japan) and 4 µl cDNA (10X). The conditions were as follows: A cycle of 50°C for 2 min, a 95°C for 10 min, followed by 40 cycles of 95°C for 30 sec and 60°C for 30 sec. The 2-ΔΔCq method was used to analyze the relative change in the expression of miR-106b (26). The primer sequences were as follows: U6, forward 5'-CGC TTC GGC AGC ACA TAT AC-3 and reverse 5'-AAA TAT GGA ACG CTT CAC GA-3'; rno-miR-106b, forward 5'-TGC GCT AAA GTG CTG ACA GTG-3' and reverse 5'-CTC AAG TGT CGT GGA GTC GGC AA-3'.

Western blot analysis

The lysates of NPCs were extracted using a RIPA buffer (Beyotime Institute of Biotechnology, Shanghai, China) and were centrifuged at 12,000 x g for 10 min at 4°C. Then 400 µl the supernatant mixed with 100 µl Laemmli buffer and was heated at 100°C for 10 min. The protein concentration was determined by using the Protein Assay kit for bicinchoninic acid (Thermo Fisher Scientific, Inc.). Electrophoresis was performed with 50 µg of total protein. Protein was resolved on a 15% SDS PAGE and transferred on to polyvinylidene difluoride membranes. Membrane transfer of the p21 protein was achieved under 200 mA for 1 h. The membrane was then immersed in 5% tris-buffered saline and tween (TBST) and incubated at room temperature for 2 h. The primary antibody rabbit anti-rat p21 (1:500; cat. no. sc-397; Santa Cruz Biotechnology, Inc., Dallas, TX, USA) was incubated overnight at 4°C for 16 h. The membrane was then fully washed with TBST, and the goat anti-rat IgG secondary antibody (1:50,000; cat. no. BA1054; Wuhan Boster Biological Technology Co., Ltd.) conjugated to HRP was used for incubation of the membrane at room temperature for 2 h. The Gene Genius Bio-Imaging system gel imager was used to capture images, and BandScan version 5.0 software (Glyko Inc., Novato, CA, USA) was used to analyze the optical density signal strips.

Statistical analysis

The experimental data are expressed as the mean ± standard deviation. All experiments were repeated at least 3 times. Differences between groups were analyzed by one-way analysis of variance followed by the LSD test. Differences between two groups were analyzed using Student's t-test. SPSS 17.0 statistical software (version 17.0; SPSS, Inc., Chicago, IL, USA) was used for statistical analysis. P<0.05 was considered to indicate a statistically significant difference.

Results

Characterization of NPCs cultured from the hippocampus

The hippocampal tissues were separated from the newborn rats. Following the first passage, the cells started to form neurospheres, which had grown to almost 100 µm on the fifth day. The neurospheres at passage 2 exhibited a smooth shiny surface under light microscopy (Fig. 1C) and positively expressed the NPC-specific marker nestin (Fig. 1D).

rTMS promotes the proliferation of NPCs in vitro

EdU staining was used to analyze NPC proliferation. The results showed that there was a higher proportion of EdU-positive cells in the rTMS group than in the sham group cells (sham, vs. rTMS, 38.1±9.5%, vs. 51.7±25.5%, P<0.01; Fig. 2A and B). These results indicated that rTMS promoted the proliferation of NPCs.

rTMS increases miR-106b and decreases p21 levels in NPCs in vitro

The results showed that the treatment of rTMS significantly upregulated the expression of miR-106b (sham, vs. rTMS, 0.87±0.15, vs. 1.18±0.21, P<0.01; Fig. 2C). As shown in the results of the western blot analysis, rTMS markedly decreased the level of p21 (sham, vs. rTMS, 0.57±0.15, vs. 0.28±0.09, P<0.05; Fig. 2D and E).

Overexpressing miR-106b further enhances the proliferation of NPCs induced by rTMS

In order to illustrate whether miR-106b is involved in the effects induced by rTMS on NPCs, the expression of miR-106b in NPCs was modulated. As shown in Fig. 3A and B, the overexpression of miR-106b increased the number of EdU-positive cells compared with the number in the cells transfected with Lenti-null, the transfection control (L106b, vs. LN, 64.3±8.6%, vs. 28.1±4.7%, P<0.01). However, the knockdown of miR-106b reduced the proliferation of NPCs (A106b, vs. NC, 18.4±5.9%, vs. 38.1±9.5%, P<0.01). rTMS further increased the proliferation of NPCs in the miR-106b overexpression group (L106bS, vs. L106b, 88.2±4.6%, vs. 64.3±8.6%, P<0.01), which was eliminated by miR-106b siRNA (A106bS, vs. A106b, 38.6±6.5%, vs. 18.4±5.9%, P<0.01). Together, these data indicate that miR-106 modulated the rTMS-induced proliferation of NPCs.

rTMS upregulates the expression of miR-106b

Subsequently, the present study examined the expression of miR-106b in each group, and found that rTMS increased miR-106b in cells of the overexpression group (L106b, vs. L106bS, 2.09±0.1, vs. 2.43±0.11, P<0.01; Fig. 4A) and knockdown group (A106b, vs. A106bS, 0.30±0.02, vs. 0.48±0.02, P<0.01; Fig. 4B).

rTMS attenuates the protein expression of p21 in NPCs

Following lentiviral infection and knockdown of miR-106b in NPCs, the protein expression of p21 was assessed by western blot analysis (Fig. 5A and B). The data showed that the level of p21 was significantly decreased by rTMS in the overexpression group (L106b, vs. L106bS, 0.40±0.03, vs. 0.24±0.05, P<0.05) and knockdown group (A106b, vs. A106bS, 0.67±0.03, vs. 0.48±0.05, P<0.05).

The results showed that miR-106b, which promoted the proliferation of cells via p21, was upregulated by rTMS. These results suggested that rTMS promotes the proliferation of NPCs via miR-106b and possibly by inhibiting the expression of p21.

Discussion

It has been shown that rTMS can induce plasticity in the brain (7,8) and can influence the gene expression profile of NPCs and cultured neural cells (27-29). As a clinical treatment, evidence from fMRI (7) and PET (8) analyses has demonstrated that rTMS alters prefrontal-hippocampal network dynamics in healthy volunteers and increases glucose metabolism in rats. It has also been found to modulate miRs in vitro (24). In the present study, it was observed that rTMS induced EdU-positive NPCs and upregulated the expression of miR-106b. Subsequently, miR-106b was either stably overexpressed or its siRNAs were transfected into NPCs, and it was confirmed that rTMS promoted the proliferation of NPCs through miR-106b and possibly by inhibiting the expression of kinase inhibitor p21. The data are presented in Fig. 2.

The protocols of rTMS are generally controversial in treatment of the nervous system (30). Stimulation frequency is the most important factor in terms of rTMS parameters. Low frequency rTMS is considered to have an inhibitory effect on the brain (26), whereas high frequency rTMS has excitatory effects (31). In animal experiments, a high frequency (>5 Hz) has been reported to promote neural plasticity and improve behavior in rats with depression (32,33) and in rats with focal cerebral ischemia (15), associated with plasticity genes, including brain-derived neurotrophic factor (BDNF) (33-35). In cell experiments, compared with low frequency (1 Hz) rTMS, high frequency (10 Hz) rTMS induced neuroprotective and anti-apoptotic effects in a cell model of hippocampal injury (36,37). In addition, high frequency (10 Hz) rTMS has been shown to induce neural plasticity in hippocampal slice cultures (31). In clinical experiments, high frequency rTMS is generally used for neuropathic pain (38,39), cognition and motor recovery in patients with Parkinson's disease and Alzheimer's disease (6), and leads to superior improvements over low frequency rTMS. The stimulation intensity is another important parameter; it decreases within the coil distance of 3.5 cm, and 60% of its intensity is maintained at a distance of 1 cm (40). Although transcranial magnetic stimulations should not be uniform on the suspended cell cultures in a dish due to the difference in distance, the electromagnetic field has been shown to be effective in inducing NPC proliferation (29). The results showed that the proliferation of NPCs was promoted by rTMS daily (1,000 stimuli) for 3 days at 10 Hz, with 1.75 T output.

The expression of miR-106b is high in the adult rat brain and influences thousands of target genes. One of these, minichromosome maintenance complex component 7, which is decreased in the brain of rats with Down's syndrome, suggests that miR-106b is closely associated with nerve generation (41). In addition, miR-106b influences the insulin/insulin-like growth factor-1-Forkhead box O pathway (19), which can promote NPC proliferation (42). Our previous study found that protein kinase inhibitor p21 as the target gene of miR-106b was another proliferative factor through regulating cyclins (24).

The molecular mechanism of p21 regulating the proliferation of NPCs remains to be fully elucidated. Cell cycle is regulated by cyclins, cyclin-dependent kinase (CDK) and CDKI (43). p21 as one of the CDKIs, is the direct target gene of miR-106b (20). It combines with CDK2, CDK4/6, cyclinA, cyclinD and cyclinE to arrest the cell cycle (44). miR-106b-med-ited p21 silencing can affect the cell cycle and promote the cells to exit the G1 stage and enter the S stage (44,45). In addition, p21 can be combined with enhancer SRY-box binding protein-2 (Sox2) regulatory region 2 (46), which is a Sox2 marker in NPCs (47). Low p21 increasing the expression of Sox2 can induce the proliferation of NPCs. Tailless (Txl) is an orphan nuclear receptor specifically expressed in NPCs and P21, as target gene of Txl, is crucial for the homeostasis of NPCs (48,49). In addition, Yoon et al (50) claimed that a therapeutic effect of rTMS on subacute cerebral ischemia rat was associated with an anti-apoptotic effect. Liu et al (51) demonstrated that miR-106b modulated the anti-apoptotic effect through inhibiting p21. Decreasing apoptosis upregulates neuronal turnover, which is beneficial for neural plasticity (52). p21 is a protector preventing premature loss of the NSC population (53); when there is a lack of p21, cells have a higher proliferative activity. In the present study, it was found that rTMS decreased the expression of p21, which was consistent with the EdU-positive cells. These data are supported by an in vivo study (16), which showed that 14 days of chronic rTMS increased the number of BrdU-positive cells in the dentate gyrus of rats. The present study did not characterize cell differentiation of the cultured NPCs in the proliferation medium, which requires examination in future investigations.

There is an equilibrium system in place to balance the generation, proliferation or differentiation of cells in the brain, and the pool of stem cells can be depleted due to a weak proliferation rate (54-56). The results of the present study suggested that rTMS assisted in maintaining the equilibrium system by the appropriate continuous growth rate of NPCs in the brain. It is reported that, in the adult hippocampus, ~700 new neurons (annual turnover rate 1.75%) are exchanged every day, with a mild decline during aging (57). Treatment including regular physical activity has been suggested to resist aging due to promoting the proliferation of NPCs associated with increasing BDNF (58,59). Taken together, neurogenesis induced by rTMS may be another method to alleviate aging, which has application prospects in future healthcare and medical treatment.

According to the data, rTMS increases miR-106b and decreases p21 levels in NPCs in vitro, which is determined by overexpressing and downregulating miR-106b expression. The present study showed that rTMS-miR-106b was the main pathway influencing the action of NPCs. In conclusion, high frequency (10 Hz) rTMS promoted NPC proliferation via upregulating miR-106b, and possibly by inhibiting the expression of p21.

Acknowledgements

Not applicable.

Funding

The study was supported by the National Natural Science Foundation of Young Scholars of China (grant no. 81700280), the Program of Natural Science Foundation of Hubei Province, China (grant no. 2017CFB361), the Outstanding Young Scientific and Technological Innovation Team in the Colleges and Universities of Hubei Province, China (grant no. T201523), the Scientific Research Project supported by Wuhan Sports University (grant no. 2016XH24), and the program of China Scholarship Council (grant no. 201708420245).

Availability of data and materials

The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

Authors' contributions

HL and GL performed experiments; HL, GL, JW and CM wrote the manuscript; all authors contributed to manuscript preparation, discussed the results, analyzed data and commented on the manuscript; HL, YC and YY developed the concepts and designed the study. All authors read and approved the final manuscript.

Ethics approval and consent to participate

All experimental procedures were approved by the ethics committee of the Wuhan Sports University (Wuhan, China).

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

References

1 

Lewis G: Transcranial magnetic stimulation for depression. Lancet. 391:1639–1640. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Hosomi K, Shimokawa T, Ikoma K, Nakamura Y, Sugiyama K, Ugawa Y, Uozumi T, Yamamoto T and Saitoh Y: Daily repetitive transcranial magnetic stimulation of primary motor cortex for neuropathic pain: A randomized, multicenter, double-blind, crossover, sham-controlled trial. Pain. 154:1065–1072. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Gersner R, Oberman L, Sanchez MJ, Chiriboga N, Kaye HL, Pascual-Leone A, Libenson M, Roth Y, Zangen A, Rotenberg A, et al: H-coil repetitive transcranial magnetic stimulation for treatment of temporal lobe epilepsy: A case report. Epilepsy Behav Case Rep. 5:52–56. 2016. View Article : Google Scholar : PubMed/NCBI

4 

Kalita J, Laskar S, Bhoi SK and Misra UK: Efficacy of single versus three sessions of high rate repetitive transcranial magnetic stimulation in chronic migraine and tension-type headache. J Neurol. 263:2238–2246. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Jiang CG, Zhang T, Yue FG, Yi ML and Gao D: Efficacy of repetitive transcranial magnetic stimulation in the treatment of patients with chronic primary insomnia. Cell Biochem Biophys. 67:169–173. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Bentwich J, Dobronevsky E, Aichenbaum S, Shorer R, Peretz R, Khaigrekht M, Marton RG and Rabey JM: Beneficial effect of repetitive transcranial magnetic stimulation combined with cognitive training for the treatment of Alzheimer's disease: A proof of concept study. J Neural Transm (Vienna). 118:463–471. 2011. View Article : Google Scholar

7 

Bilek E, Schäfer A, Ochs E, Esslinger C, Zangl M, Plichta MM, Braun U, Kirsch P, Schulze TG, Rietschel M, et al: Application of high-frequency repetitive transcranial magnetic stimulation to the DLPFC alters human prefrontal-hippocampal functional interaction. J Neurosci. 33:7050–7056. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Lee SA, Oh BM, Kim SJ and Paik NJ: The molecular evidence of neural plasticity induced by cerebellar repetitive transcranial magnetic stimulation in the rat brain: A preliminary report. Neurosci Lett. 575:47–52. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Touge T, Gerschlager W, Brown P and Rothwell JC: Are the after-effects of low-frequency rTMS on motor cortex excitability due to changes in the efficacy of cortical synapses? Clin Neurophysiol. 112:2138–2145. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Liu Y, Yang H, Tang X, Bai W, Wang G and Tian X: Repetitive transcranial magnetic stimulation regulates L-type Ca(2+) channel activity inhibited by early sevoflurane exposure. Brain Res. 1646:207–218. 2016. View Article : Google Scholar : PubMed/NCBI

11 

Zhang N, Xing M, Wang Y, Tao H and Cheng Y: Repetitive transcranial magnetic stimulation enhances spatial learning and synaptic plasticity via the VEGF and BDNF-NMDAR pathways in a rat model of vascular dementia. Neuroscience. 311:284–289. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Ming GL and Song H: Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci. 28:223–250. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Müller-Dahlhaus F and Ziemann U: Metaplasticity in human cortex. Neuroscientist. 21:185–202. 2015. View Article : Google Scholar

14 

Ueyama E, Ukai S, Ogawa A, Yamamoto M, Kawaguchi S, Ishii R and Shinosaki K: Chronic repetitive transcranial magnetic stimulation increases hippocampal neurogenesis in rats. Psychiatry Clin Neurosci. 65:77–81. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Guo F, Han X, Zhang J, Zhao X, Lou J, Chen H and Huang X: Repetitive transcranial magnetic stimulation promotes neural stem cell proliferation via the regulation of miR-25 in a rat model of focal cerebral ischemia. PLoS One. 9:e1092672014. View Article : Google Scholar : PubMed/NCBI

16 

Zeng Y, Yi R and Cullen BR: Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha. EMBO J. 24:138–148. 2005. View Article : Google Scholar :

17 

Chen H, Qian K, Tang ZP, Xing B, Chen H, Liu N, Huang X and Zhang S: Bioinformatics and microarray analysis of microRNA expression profiles of murine embryonic stem cells, neural stem cells induced from ESCs and isolated from E8.5 mouse neural tube. Neurol Res. 32:603–613. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Anokye-Danso F, Snitow M and Morrisey EE: How microRNAs facilitate reprogramming to pluripotency. J Cell Sci. 125:4179–4187. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Brett JO, Renault VM, Rafalski VA, Webb AE and Brunet A: The microRNA cluster miR-106b~25 regulates adult neural stem/progenitor cell proliferation and neuronal differentiation. Aging (Albany NY). 3:108–124. 2011. View Article : Google Scholar

20 

Ivanovska I, Ball AS, Diaz RL, Magnus JF, Kibukawa M, Schelter JM, Kobayashi SV, Lim L, Burchard J, Jackson AL, et al: MicroRNAs in the miR-106b family regulate p21/CDKN1A and promote cell cycle progression. Mol Cell Biol. 28:2167–2174. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Karimian A, Ahmadi Y and Yousefi B: Multiple functions of p21 in cell cycle, apoptosis and transcriptional regulation after DNA damage. DNA Repair (Amst). 42:63–71. 2016. View Article : Google Scholar

22 

Wang H, Zhu LJ, Yang YC, Wang ZX and Wang R: MiR-224 promotes the chemoresistance of human lung adenocarcinoma cells to cisplatin via regulating G1/S transition and apoptosis by targeting p21(WAF1/CIP1). Br J Cancer. 111:339–354. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Semaan A, Qazi AM, Seward S, Chamala S, Bryant CS, Kumar S, Morris R, Steffes CP, Bouwman DL, Munkarah AR, et al: MicroRNA-101 inhibits growth of epithelial ovarian cancer by relieving chromatin-mediated transcriptional repression of p21(waf1/cip1). Pharm Res. 28:3079–3090. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Liu H, Han XH, Chen H, Zheng CX, Yang Y and Huang XL: Repetitive magnetic stimulation promotes neural stem cells proliferation by upregulating MiR-106b in vitro. J Huazhong Univ Sci Technolog Med Sci. 35:766–772. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Reynolds BA and Weiss S: Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science. 255:1707–1710. 1992. View Article : Google Scholar : PubMed/NCBI

26 

Casula EP, Tarantino V, Basso D, Arcara G, Marino G, Toffolo GM, Rothwell JC and Bisiacchi PS: Low-frequency rTMS inhibitory effects in the primary motor cortex: Insights from TMS-evoked potentials. Neuroimage. 98:225–232. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Cash RFH, Dar A, Hui J, De Ruiter L, Baarbé J, Fettes P, Peters S, Fitzgerald PB, Downar J and Chen R: Influence of inter-train interval on the plastic effects of rTMS. Brain Stimul. 10:630–636. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Stock M, Kirchner B, Waibler D, Cowley DE, Pfaffl MW and Kuehn R: Effect of magnetic stimulation on the gene expression profile of in vitro cultured neural cells. Neurosci Lett. 526:122–127. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Cui M, Ge H, Zhao H, Zou Y, Chen Y and Feng H: Electromagnetic fields for the regulation of neural stem cells. Stem Cells Int. 2017:98984392017. View Article : Google Scholar : PubMed/NCBI

30 

Barker AT, Freeston IL, Jalinous R and Jarratt JA: Magnetic stimulation of the human brain and peripheral nervous system: An introduction and the results of an initial clinical evaluation. Neurosurgery. 20:100–109. 1987. View Article : Google Scholar : PubMed/NCBI

31 

Vlachos A, Müller-Dahlhaus F, Rosskopp J, Lenz M, Ziemann U and Deller T: Repetitive magnetic stimulation induces functional and structural plasticity of excitatory postsynapses in mouse organotypic hippocampal slice cultures? J Neurosci. 21:17514–17523. 2012. View Article : Google Scholar

32 

Sun P, Wang F, Wang L, Zhang Y, Yamamoto R, Sugai T, Zhang Q, Wang Z and Kato N: Increase in cortical pyramidal cell excitability accompanies depression-like behavior in mice: A transcranial magnetic stimulation study. J Neurosci. 31:16464–16472. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Samuels BA and Hen R: Neurogenesis and affective disorders. Eur J Neurosci. 33:1152–1159. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Bakker N, Shahab S, Giacobbe P, Blumberger DM, Daskalakis ZJ, Kennedy SH and Downar J: rTMS of the dorsomedial prefrontal cortex for major depression: Safety, tolerability, effectiveness, and outcome predictors for 10 Hz versus intermittent theta-burst stimulation. Brain Stimul. 8:208–215. 2015. View Article : Google Scholar

35 

Uhm KE, Kim YH, Yoon KJ, Hwang JM and Chang WH: BDNF genotype influence the efficacy of rTMS in stroke patients. Neurosci Lett. 594:117–121. 2015. View Article : Google Scholar : PubMed/NCBI

36 

Post A, Müller MB, Engelmann M and Keck ME: Repetitive transcranial magnetic stimulation in rats: Evidence for a neuroprotective effect in vitro and in vivo. Eur J Neurosci. 11:3247–3254. 1999. View Article : Google Scholar : PubMed/NCBI

37 

Aydin-Abidin S, Trippe J, Funke K, Eysel UT and Benali A: High- and low-frequency repetitive transcranial magnetic stimulation differentially activates c-Fos and zif268 protein expression in the rat brain. Exp Brain Res. 188:249–261. 2008. View Article : Google Scholar : PubMed/NCBI

38 

Lefaucheur JP, Drouot X, Ménard-Lefaucheur I, Keravel Y and Nguyen JP: Motor cortex rTMS restores defective intracortical inhibition in chronic neuropathic pain. Neurology. 67:1568–1574. 2006. View Article : Google Scholar : PubMed/NCBI

39 

Cruccu G, Aziz TZ, Garcia-Larrea L, Hansson P, Jensen TS, Lefaucheur JP, Simpson BA and Taylor RS: A meta-analysis neurostimulation therapy for neuropathic pain. Eur J Neurol. 14:952–970. 2007. View Article : Google Scholar : PubMed/NCBI

40 

Grehl S, Martina D, Goyenvalle C, Deng ZD, Rodger J and Sherrard RM: In vitro magnetic stimulation: A simple stimulation device to deliver defined low intensity electromagnetic fields. Front Neural Circuits. 10:852016. View Article : Google Scholar :

41 

Hewitt CA, Ling KH, Merson TD, Simpson KM, Ritchie ME, King SL, Pritchard MA, Smyth GK, Thomas T, Scott HS and Voss AK: Gene network disruptions and neurogenesis defects in the adult Ts1Cje mouse model of Down syndrome. PLoS One. 5:e115612010. View Article : Google Scholar : PubMed/NCBI

42 

Kouroupi G, Lavdas AA, Gaitanou M, Thomaidou D, Stylianopoulou F and Matsas R: Lentivirus-mediated expression of insulin-like growth factor-I promotes neural stem/precursor cell proliferation and enhances their potential to generate neurons. J Neurochem. 115:460–474. 2010. View Article : Google Scholar : PubMed/NCBI

43 

Sherr CJ and Roberts JM: Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev. 9:1149–1163. 1995. View Article : Google Scholar : PubMed/NCBI

44 

Denicourt C and Dowdy SF: Cip/Kip proteins: More than just CDKs inhibitors. Genes Dev. 18:851–855. 2004. View Article : Google Scholar : PubMed/NCBI

45 

Ilyin GP, Glaise D, Gilot D, Baffet G and Guguen-Guillouzo C: Regulation and role of p21 and p27 cyclin-dependent kinase inhibitors during hepatocyte differentiation and growth. Am J Physiol Gastrointest Liver Physiol. 285:G115–G127. 2003. View Article : Google Scholar : PubMed/NCBI

46 

Marqués-Torrejón MÁ, Porlan E, Banito A, Gómez-Ibarlucea E, Lopez-Contreras AJ, Fernández-Capetillo O, Vidal A, Gil J, Torres J and Fariñas I: Cyclin-dependent kinase inhibitor p21 controls adult neural stem cell expansion by regulating Sox2 gene expression. Cell Stem Cell. 12:88–100. 2013. View Article : Google Scholar :

47 

Arnold K, Sarkar A, Yram MA, Polo JM, Bronson R, Sengupta S, Seandel M, Geijsen N and Hochedlinger K: Sox2(+) adult stem and progenitor cells are important for tissue regeneration and survival of mice. Cell Stem Cell. 9:317–329. 2011. View Article : Google Scholar : PubMed/NCBI

48 

Wang Y, Liu HK and Schütz G: Role of the nuclear receptor Tailless in adult neural stem cells. Mech Dev. 130:388–390. 2013. View Article : Google Scholar : PubMed/NCBI

49 

Liu HK, Belz T, Bock D, Takacs A, Wu H, Lichter P, Chai M and Schütz G: The nuclear receptor tailless is required for neurogenesis in the adult subventricular zone. Genes Dev. 22:2473–2478. 2008. View Article : Google Scholar : PubMed/NCBI

50 

Yoon KJ, Lee YT and Han TR: Mechanism of functional recovery after repetitive transcranial magnetic stimulation (rTMS) in the subacute cerebral ischemic rat model: Neural plasticity or anti-apoptosis? Exp Brain Res. 214:549–556. 2011. View Article : Google Scholar : PubMed/NCBI

51 

Liu Z, Yang D, Xie P, Ren G, Sun G, Zeng X and Sun X: MiR-106b and MiR-15b modulate apoptosis and angiogenesis in myocardial infarction. Cell Physiol Biochem. 29:851–862. 2012. View Article : Google Scholar : PubMed/NCBI

52 

Chambers RA, Potenza MN, Hoffman RE and Miranker W: Simulated apoptosis/neurogenesis regulates learning and memory capabilities of adaptive neural networks. Neuropsychopharmacology. 29:747–758. 2004. View Article : Google Scholar : PubMed/NCBI

53 

Leslie KF: p21: Protector of progenitor pools. Science Signal. 6:ec2732013. View Article : Google Scholar

54 

Kippin TE, Martens DJ and van der Kooy D: p21 loss compromises the relative quiescence of forebrain stem cell proliferation leading to exhaustion of their proliferation capacity. Genes Dev. 19:756–767. 2005. View Article : Google Scholar : PubMed/NCBI

55 

Orford KW and Scadden DT: Deconstructing stem cell self-renewal: Genetic insights into cell-cycle regulation. Nat Rev Genet. 9:115–128. 2008. View Article : Google Scholar : PubMed/NCBI

56 

Paik JH, Ding Z, Narurkar R, Ramkissoon S, Muller F, Kamoun WS, Chae SS, Zheng H, Ying H, Mahoney J, et al: FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis. Cell Stem Cell. 5:540–553. 2009. View Article : Google Scholar : PubMed/NCBI

57 

Spalding KL, Bergmann O, Alkass K, Bernard S, Salehpour M, Huttner HB, Boström E, Westerlund I, Vial C, Buchholz BA, et al: Dynamics of hippocampal neurogenesis in adult humans. Cell. 153:1219–1227. 2013. View Article : Google Scholar : PubMed/NCBI

58 

Kronenberg G, Reuter K, Steiner B, Brandt MD, Jessberger S, Yamaguchi M and Kempermann G: Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuli. J Comp Neurol. 467:455–463. 2003. View Article : Google Scholar : PubMed/NCBI

59 

Nam SM, Kim JW, Yoo DY, Yim HS, Kim DW, Choi JH, Kim W, Jung HY, Won MH, Hwang IK, et al: Physical exercise ameliorates the reduction of neural stem cell, cell proliferation and neuroblast differentiation in senescent mice induced by D-galactose. BMC Neurosci. 15:1162014. View Article : Google Scholar : PubMed/NCBI

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December-2018
Volume 42 Issue 6

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Online ISSN:1791-244X

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Spandidos Publications style
Liu H, Li G, Ma C, Chen Y, Wang J and Yang Y: Repetitive magnetic stimulation promotes the proliferation of neural progenitor cells via modulating the expression of miR-106b. Int J Mol Med 42: 3631-3639, 2018
APA
Liu, H., Li, G., Ma, C., Chen, Y., Wang, J., & Yang, Y. (2018). Repetitive magnetic stimulation promotes the proliferation of neural progenitor cells via modulating the expression of miR-106b. International Journal of Molecular Medicine, 42, 3631-3639. https://doi.org/10.3892/ijmm.2018.3922
MLA
Liu, H., Li, G., Ma, C., Chen, Y., Wang, J., Yang, Y."Repetitive magnetic stimulation promotes the proliferation of neural progenitor cells via modulating the expression of miR-106b". International Journal of Molecular Medicine 42.6 (2018): 3631-3639.
Chicago
Liu, H., Li, G., Ma, C., Chen, Y., Wang, J., Yang, Y."Repetitive magnetic stimulation promotes the proliferation of neural progenitor cells via modulating the expression of miR-106b". International Journal of Molecular Medicine 42, no. 6 (2018): 3631-3639. https://doi.org/10.3892/ijmm.2018.3922