Frequency-specific effects of repetitive magnetic stimulation on primary astrocyte cultures

Clarke, Darren; Penrose, Marissa A.; Penstone, Tamasin; Fuller-Carter, Paula I.; Hool, Livia C.; Harvey, Alan R.; Rodger, Jennifer; Bates, Kristyn A.

doi:10.3233/rnn-160708

Cited by 15 publications

(24 citation statements)

References 57 publications

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“…Thus, our stimulation protocol likely induced action potentials in some pyramidal neurons, mostly in the superficial layers of the cortex, but did not directly activate thalamic neurons. However, E-field values below the threshold value required to produce action potentials have been observed inducing non-synaptic mechanisms of neuroplasticity such as structural reoganisation (Makowiecki et al, 2014), increased neurogenesis (Heath et al, 2018), gene regulation and increased intracellular calcium (Grehl et al, 2015;Clarke et al, 2017b), altered neuron excitability (Tang et al, 2016;Makowiecki et al, 2018), and glial changes (Clarke et al, 2017a;Cullen et al, 2019). Therefore, we cannot rule out that non-synaptic mechanisms of plasticity induced in the thalamus by low intensity magnetic fields may contribute to the changes in firing parameters that we report here.…”

Section: Discussionmentioning

confidence: 66%

Excitatory Repetitive Transcranial Magnetic Stimulation Over Prefrontal Cortex in a Guinea Pig Model Ameliorates Tinnitus

et al. 2021

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Tinnitus, a phantom auditory perception that can seriously affect quality of life, is generally triggered by cochlear trauma and associated with aberrant activity throughout the auditory pathways, often referred to as hyperactivity. Studies suggest that non-auditory structures, such as prefrontal cortex (PFC), may be involved in tinnitus generation, by affecting sensory gating in auditory thalamus, allowing hyperactivity to reach the cortex and lead to perception. Indeed, human studies have shown that repetitive transcranial magnetic stimulation (rTMS) of PFC can alleviate tinnitus. The current study investigated whether this therapeutic effect is achieved through inhibition of thalamic hyperactivity, comparing effects of two common clinical rTMS protocols with sham treatment, in a guinea pig tinnitus model. Animals underwent acoustic trauma and once tinnitus developed were treated with either intermittent theta burst stimulation (iTBS), 20 Hz rTMS, or sham rTMS (10 days, 10 min/day; weekdays only). Tinnitus was reassessed and extracellular recordings of spontaneous tonic and burst firing rates in auditory thalamus made. To verify effects in PFC, densities of neurons positive for calcium-binding proteins, calbindin and parvalbumin, were investigated using immunohistochemistry. Both rTMS protocols significantly reduced tinnitus compared to sham. However, spontaneous tonic firing decreased following 20 Hz stimulation and increased following iTBS in auditory thalamus. Burst rate was significantly different between 20 Hz and iTBS stimulation, and burst duration was increased only after 20 Hz treatment. Density of calbindin, but not parvalbumin positive neurons, was significantly increased in the most dorsal region of PFC indicating that rTMS directly affected PFC. Our results support the involvement of PFC in tinnitus modulation, and the therapeutic benefit of rTMS on PFC in treating tinnitus, but indicate this is not achieved solely by suppression of thalamic hyperactivity.

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Section: Discussionmentioning

confidence: 66%

Excitatory Repetitive Transcranial Magnetic Stimulation Over Prefrontal Cortex in a Guinea Pig Model Ameliorates Tinnitus

et al. 2021

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“…Furthermore, astrocytes regulate several neuronal protective mechanisms known to be modulated by rTMS (Becerra‐Calixto & Cardona‐Gómez, 2017). Despite this, so far, few studies have explored the impact of rTMS on glial cells, being the existing data inconclusive (Clarke et al., 2017). Reports from pre‐clinical models indicate that HF‐rTMS induce astrocyte activation (Chan et al., 1999; Raus et al., 2013) and proliferation (Medina‐Fernandez et al., 2017), but also that it has no effect (Czéh et al., 2002; Kim et al., 2013; Sasso et al., 2016; Yang et al., 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Statistical analysis was performed using two-way ANOVA followed by Bonferroni's post hoc test. **p < 0.01 and ***p < 0.01 compared to control; ##p < 0.01 compared to OGD/R; $$$p < 0.001 compared to control HF-rMS (Clarke et al, 2017). Reports from pre-clinical models indicate that HF-rTMS induce astrocyte activation (Chan et al, 1999;Raus et al, 2013) and proliferation (Medina-Fernandez et al, 2017), but also that it has no effect (Czéh et al, 2002;Kim et al, 2013;Sasso et al, 2016;Yang et al, 2018).…”

Section: F I G U R Ementioning

confidence: 98%

Astrocytes contribute to the neuronal recovery promoted by high‐frequency repetitive magnetic stimulation in in vitro models of ischemia

Roque

Pinto

Patto

et al. 2021

J of Neuroscience Research

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After decades of effort, there are no effective clinical treatments to induce the recovery of ischemia-injured tissues, and among the several strategies that have been explored, repetitive transcranial magnetic stimulation has proven to be one of the most promising, with beneficial effects in limb motor function, aphasia, hemispatial neglect, or dysphagia. Despite the clinical evidences, little is known about the mechanisms underlying those effects. The present study aimed to explore the cellular and molecular effects of high-frequency repetitive magnetic stimulation (HF-rMS) on an in vitro model of ischemia. Using primary cortical cultures exposed to oxygen and glucose deprivation followed by reperfusion, we observed that HF-rMS treatment prevents the ischemia-induced neuronal death by 21.2%, and the neurite degeneration triggered by ischemia. Our results also demonstrate that with this treatment there is an increase of 89.2% on the number cells expressing ERK1/2, of 20.1% on the number of cells expressing c-Fos, and a synaptogenic effect, through an increase of 62.9% in the number of synaptic puncta as well as of 49.4% in their intensity. Interestingly, our results indicate that astrocytes are crucial to the beneficial effects triggered by HF-rMS after ischemia, thus suggesting a direct effect of HF-rMS on these cells. The modulation of astrocytes with this non-invasive brain stimulation technique is a promising approach to promote the recovery of ischemia-induced injured tissues; however, it is essential to understand how these effects can be modulated in order to optimize the protocols and enhance the beneficial outcomes.

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“…Studies assessing the influence of EMF on ATP signaling and intra- and extracellular Ca 2+ in astrocytes are scarce, have been made with extremely low frequency magnetic fields (ELF-MF) and ELF-EMF, respectively (34,85), and look at in vitro astrocyte cultures. However, computational models that studied the influence of EEG field on calcium waves in the neocortex (39) do suggest potential effects of ELF-MF, ELF-EMF, and EEG on ATP signaling and extracellular Ca 2+ concentration in astrocytes.…”

Section: Resultsmentioning

confidence: 99%

“…While Clarke et al (85) have shown that ELF-MFs increase intracellular calcium levels within the cytoplasm of the cultured astrocytes, Golfert et al (34), by studying microvesicle motility of astrocytes in in vitro cultures, have also suggested that ELF-EMFs change calcium levels by increasing calcium influx. Increased Ca 2+ ion influx is usually a product of astrocytic induction of diffusion of IP3 through gap junctions and extracellular ATP signaling and, in normal conditions, it activates the surrounding microglial cells and changes astrocytes’ morphology and mobility.…”

Section: Resultsmentioning

confidence: 99%

Molecular mechanisms of microglia- and astrocyte-driven neurorestoration triggered by application of electromagnetic fields

Isakovic¹,

Gorup

Mitrečić

2019

Croat Med J

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Aim To propose potential mechanisms of action of electromagnetic fields (EMF) on astrocytes and microglia and to elucidate the role of heat shock proteins (HSP), adenosine triphosphate (ATP), calcium ions (Ca 2+ ), and hypoxia-inducible factor 1α (HIF1α) in neurorestoration following the application of EMF. Methods We reviewed the existing studies within the public domain and cross-evaluated their results in order to conclude on the molecular mechanisms of microglia-astrocyte crosstalk at work during EMF treatment. Results The existing studies suggest that EMF induces the increase of HSP70 expression and inhibition of HIF1α, thus decreasing inflammation and allowing the microglia-astrocyte crosstalk to initiate the formation of a glial scar within the central nervous system. Furthermore, by potentially up-regulating A2A and A3 adenosine receptors, EMF increases cAMP accumulation from astrocytes and reduces the expression of inflammatory cytokines TNF α and IL-8, thus initiating neurorestoration. Conclusion The microglia-astrocyte crosstalk during EMF treatment is crucial for the initiation of neurorestoration. Elucidating the exact mechanisms of EMF actions upon microglia and astrocytes, and its role in neurorestoration, could be a key step in further research of the therapeutic potential of EMFs in various neurological disorders.

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Frequency-specific effects of repetitive magnetic stimulation on primary astrocyte cultures

Abstract: Our results provide preliminary evidence that rMS can influence astrocyte physiology, indicating the potential for a novel mechanism by which rTMS can influence brain activity.

Cited by 15 publications

References 57 publications

Excitatory Repetitive Transcranial Magnetic Stimulation Over Prefrontal Cortex in a Guinea Pig Model Ameliorates Tinnitus

Excitatory Repetitive Transcranial Magnetic Stimulation Over Prefrontal Cortex in a Guinea Pig Model Ameliorates Tinnitus

Astrocytes contribute to the neuronal recovery promoted by high‐frequency repetitive magnetic stimulation in in vitro models of ischemia

Molecular mechanisms of microglia- and astrocyte-driven neurorestoration triggered by application of electromagnetic fields

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