Low-intensity pulsed ultrasound (LIPUS) has been reported to enhance proliferation and to alter protein production in various kinds of cells. In the present study, we measured the neurites length after LIPUS treatment to define the effectiveness of LIPUS stimulation on neurons, and then we examined the acticity of GSK-3beta to study the intracellular mechanism of neurite's outgrowth.
LIPUS was applied to cultured primary rat cortical neurons for 5 minutes every day with spatial- and temporal average intensities (SATA) of 10 mW/cm(2), a pulse width of 200 microseconds, a repetition rate of 1.5 KHz, and an operation frequency of 1 MHz. Neurons were photographed on the third day after LIPUS treatment and harvested at third, seventh, and tenth days for immunoblot and semi-quantitative RT-PCR analysis.
Morphology change showed that neurite extension was enhanced by LIPUS. There was also a remarkable decrease of proteins, including p-Akt, p-GSK-3beta, and p-CRMP-2, observed on the seventh and tenth days, and of GSK-3beta mRNA expression, observed on the seventh day, in neurons treated with LIPUS.
LIPUS can enhance elongation of neurites and it is possible through the decreased expression of GSK-3beta.
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"As such, ultrasound could have a stimulatory influence on neuronal growth dynamics, although it is acting as a repulsive cue during exposure. This conclusion is in agreement with a recent study that demonstrated how daily exposure to ultrasound can enhance neurite elongation in developing neuronal cells (Ren et al. 2010). In terms of the biophysical mechanism responsible for ultrasound-induced neuronal morphological changes, our results have shown that mechanotransduction is likely to be involved, as blockage of stretch-activated ion channels has led to significant suppression of ultrasound-induced morphological changes (Fig. 7). "
[Show abstract][Hide abstract]ABSTRACT: Neuronal development is known to be a dynamic process that can be modulated by presenting guidance cues to neuronal cells. We show that ultrasound, when applied at pulsed settings and with intensities slightly greater than clinical diagnosis levels, can potentially act as a repulsive cue for modulating neuronal growth dynamics. Using differentiated Neuro-2a cells as the model, we have examined in vitro how neuronal development can change during and after exposure to 1-MHz ultrasound for different acoustic settings. Neurite retraction and cell body shrinkage were found in neuronal cells over a 10-min exposure period with 1.168 W/cm(2) spatial-peak, time-averaged intensity (based on 0.84 MPa peak acoustic pressure, 100-cycle pulse duration, and 500-Hz pulse repetition frequency). These effects were found to result in instances of neuronal cell body displacement. The extent of the effects was dependent on acoustic intensity, with peak acoustic pressure being a more important contributing factor compared with pulse duration. The morphological changes were found to be non-destructive, in that post-exposure neurite outgrowth and neuritogenesis were respectively observed in neurite-bearing and neurite-less neuronal cells. Our results also showed that mechanotransduction might be involved in mediating ultrasound-neuron interactions, as the morphological changes were suppressed if stretch-activated ion channels were blocked or if calcium messenger ions were chelated. Overall, these findings suggest that ultrasound can potentially influence how neuronal cells develop through modifying their cytomechanical characteristics.
Full-text · Article · Feb 2013 · Ultrasound in medicine & biology
"From these findings, we postulate that when neurons are irradiated by LIPUS, an unknown intracellular mechanism may be activated as a response to this " injury " and, consequently, neurons reduce the mRNA expression of GSK-3. The decrease of GSK-3beta activity comes from reduced expression, but not through the PI3-kinase/Akt/GSK-3 signaling pathway (Ren, Li et al. 2010). "