Induction of Neuritogenesis in PC12 Cells by a Pulsed Electromagnetic Field via MEK-ERK1/2 Signaling

Kudo, Tada Aki; Kanetaka, Hiroyasu; Shimizu, Yoshinaka; Abe, Toshihiko; Mori, Hitoshi; Mori, Kazumi; Suzuki, Eizaburo; Takagi, Toshiyuki; Izumi, Shin Ichi

doi:10.1247/csf.12030

Cited by 20 publications

(14 citation statements)

References 23 publications

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“…This finding suggests that longest neurites and shorter dendrites are differentially affected by MS, with more effects on longest neurites than on shorter shorter dendrites. Similar results have been reported in other studies and may be attributable to signaling pathways, microtubule composition, glutamate receptor distribution and calcium dynamics that separately affect the development of axons and dendrites (Atwal et al, 2000; Dijkhuizen and Ghosh, 2005; Kuczewski et al, 2009; Kudo et al, 2013; Mattson, 1999). …”

Section: Discussionsupporting

confidence: 90%

Differential intensity-dependent effects of magnetic stimulation on the longest neurites and shorter dendrites in neuroscreen-1 cells

Lin

Huang

et al. 2015

J. Neural Eng.

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OBJECTIVE Magnetic stimulation (MS) is a potential treatment for neuropsychiatric disorders. This study investigates whether MS-regulated neuronal activity can translate to specific changes in neuronal arborization and thus regulate synaptic activity and function. APPROACH To test our hypotheses, we examined the effects of MS on neurite growth of Neuroscreen-1 (NS-1) cells over pulse frequencies of 1, 5 and 10 Hz at field intensities controlled by machine output (MO). Cells were treated with either 30% or 40% MO and received either maximal or minimal MS-induced current-density. Due to the nature of circular MS coils, the center region of the gridded coverslip (zone 1) received minimal (~5%) electromagnetic current density while the remaining area (zone 2) received maximal (~95%) current density. Plated NS-1 cells were exposed to MS twice per day for 3 days and then evaluated for length and number of neurites and expression of brain-derived neurotrophic factor (BDNF). MAIN RESULTS We show that MS dramatically affects the growth of the longest neurites (axon-like) but does not significantly affect the growth of shorter neurites (dendrite-like). Also, MS-induced changes in the longest neurite growth were most evident in zone 1, but not in zone 2. MS effects were intensity-dependent and were most evident in the bolstering of the longest neurite outgrowth, mainly seen in the 10 Hz MS group. Furthermore, we found that MS-increased BDNF expression and secretion was also frequency-dependent. Taken together, our results show that MS exerts distinct effects when different frequencies and intensities are applied to the neuritic compartments (longest neurite versus shorter dendrite(s)) of NS-1 cells. SIGNIFICANCE These findings support the concept that MS increases BDNF expression and signaling, which sculpts longest neurite arborization and connectivity by which neuronal activity is regulated. Understanding the mechanisms underlying MS is crucial for efficiently incorporating its use into potential therapeutic strategies.

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Section: Discussionsupporting

confidence: 90%

Differential intensity-dependent effects of magnetic stimulation on the longest neurites and shorter dendrites in neuroscreen-1 cells

Lin

Huang

et al. 2015

J. Neural Eng.

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“…However, the TJ107/NGF combination was ineffective. Our results differ from those of a previous study that analyzed oxaliplatin-induced neuropathy, though it is important to note that paclitaxel and oxaliplatin are very different drugs and induce neuropathy differently [13]. Oxaliplatin impairs the nerve cells themselves, whereas paclitaxel impairs the neuraxon [14].…”

Section: Discussioncontrasting

confidence: 99%

Kamishoyosan and Shakuyakukanzoto promote recovery from paclitaxel-induced neurite retraction in PC12 cells

Konaka

Moriyama

Sakurada

et al. 2017

J Pharm Health Care Sci

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BackgroundIn chemotherapy, the full round of treatment must be completed as scheduled to achieve the strongest therapeutic effect. However, peripheral neuropathy, a severe side effect of the chemotherapeutic agent paclitaxel, can force the premature discontinuation of treatment. As some kampo practitioners have suggested that it may be possible to counteract such side effects, we analyzed the effects of Kamishoyosan, Shakuyakukanzoto, and Goshajinkigan in an in vitro model of paclitaxel-induced peripheral neuropathy.MethodsPaclitaxel-treated PC12 cells were assessed for neurite length and performed Western blot analysis for growth-associated protein-43 (GAP-43) and light neurofilament protein (NF-L) levels in the presence of nerve growth factor (NGF); they were re-assessed, with additional testing for acetylcholinesterase levels, after application of one of the kampo. We also compared phosphorylation of extracellular signal-regulated kinase (Erk)1/2 and Akt via Western blot analysis. About effect of kampo to anticancer efficacy, we confirmed cell cytotoxicity in A549 cells using MTT assay.ResultsAddition of Kamishoyosan or Shakuyakukanzoto, but not Goshajinkigan, significantly improved neurite length and GAP-43 and NF-L levels from paclitaxel-treated PC12 cells, relative to those of only NGF-treated PC12 cells. The promoting effect of Kamishoyosan and Shakuyakukanzoto in neurite outgrowth is confirmed when NGF promoted neurite outgrowth, and it was inhibited partially when Erk1/2 and Akt were blocked by Erk1/2 inhibitor or Akt inhibitor alone. Furthermore, neurite outgrowth induced by TJ24 and TJ68 was inhibited more strongly when Erk1/2 inhibitor and Akt inhibitor were treated at the same time. NGF with Kamishoyosan or Shakuyakukanzoto promoted the proportion of phosphorylated Erk1/2 and phosphorylated Akt compare with NGF only. On the other hand, Kamishoyosan or Shakuyakukanzoto didn’t influence cytotoxicity of paclitaxel in A549 cells.ConclusionsKamishoyosan or Shakuyakukanzoto promotes neurite outgrowth with NGF via increasing the proportion of phosphorylated Erk1/2 and phosphorylated Akt in PC12 cells. The effect applies to recovery from paclitaxel-induced axonal involvement and might promote recovery from paclitaxel-induced neuropathy without influence of anticancer effect of paclitaxel.

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“…Neurite elongation was less than 3% in PC12 cells incubated without stimulation for 7 days (Fig 3B–3G). Treatment with BMP4, an inducer of neurite outgrowth in neurons and PC12 cells [10,23], induced neuritogenesis by day 7 (Fig 3F and 3G). No significant enhancement in neuritogenesis was observed on day 7 in PC12 cells exposed to TRTS for 6 h per day (Fig 3C–3G).…”

Section: Resultsmentioning

confidence: 99%

Induction of Neurite Outgrowth in PC12 Cells Treated with Temperature-Controlled Repeated Thermal Stimulation

et al. 2015

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To promote the functional restoration of the nervous system following injury, it is necessary to provide optimal extracellular signals that can induce neuronal regenerative activities, particularly neurite formation. This study aimed to examine the regulation of neuritogenesis by temperature-controlled repeated thermal stimulation (TRTS) in rat PC12 pheochromocytoma cells, which can be induced by neurotrophic factors to differentiate into neuron-like cells with elongated neurites. A heating plate was used to apply thermal stimulation, and the correlation of culture medium temperature with varying surface temperature of the heating plate was monitored. Plated PC12 cells were exposed to TRTS at two different temperatures via heating plate (preset surface temperature of the heating plate, 39.5°C or 42°C) in growth or differentiating medium for up to 18 h per day. We then measured the extent of growth, neuritogenesis, or acetylcholine esterase (AChE) activity (a neuronal marker). To analyze the mechanisms underlying the effects of TRTS on these cells, we examined changes in intracellular signaling using the following: tropomyosin-related kinase A inhibitor GW441756; p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580; and MAPK/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor U0126 with its inactive analog, U0124, as a control. While a TRTS of 39.5°C did not decrease the growth rate of cells in the cell growth assay, it did increase the number of neurite-bearing PC12 cells and AChE activity without the addition of other neuritogenesis inducers. Furthermore, U0126, and SB203580, but not U0124 and GW441756, considerably inhibited TRTS-induced neuritogenesis. These results suggest that TRTS can induce neuritogenesis and that participation of both the ERK1/2 and p38 MAPK signaling pathways is required for TRTS-dependent neuritogenesis in PC12 cells. Thus, TRTS may be an effective technique for regenerative neuromedicine.

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Induction of Neuritogenesis in PC12 Cells by a Pulsed Electromagnetic Field via MEK-ERK1/2 Signaling

Cited by 20 publications

References 23 publications

Differential intensity-dependent effects of magnetic stimulation on the longest neurites and shorter dendrites in neuroscreen-1 cells

Differential intensity-dependent effects of magnetic stimulation on the longest neurites and shorter dendrites in neuroscreen-1 cells

Kamishoyosan and Shakuyakukanzoto promote recovery from paclitaxel-induced neurite retraction in PC12 cells

Induction of Neurite Outgrowth in PC12 Cells Treated with Temperature-Controlled Repeated Thermal Stimulation

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