Biophysical stimulation induce demyelination via an integrin-dependent mechanism
Annals of Neurology , 04/13/2012
Lin MY et al. – The results indicate that myelin is sensitive to Chronic nerve compression (CNC) injury and support the novel concept that myelinating co–cultures respond directly to mechanical loading via activating an integrin signaling cascade.Methods
- The authors used a previously described in-vitro model of CNC injury where myelinating neuron-Schwann cell co-cultures were subjected to independent manipulations of hydrostatic pressure, hypoxia, and glucose deprivation in a custom bioreactor.
- They assessed whether demyelination increased in response to applied manipulation and determined whether integrin associated signaling cascades are upregulated.
- Hydrostatic compression of neural tissue for 24 hours induced Schwann cell proliferation without neuronal or glial cytotoxicity or apoptosis whereas hydrostatic pressure induced demyelination.
- Although glucose deprivation and hypoxia independently had minor effects on myelin stability, together they potentiated the demyelinating effects of hydrostatic compression, and in combinations, significantly destabilized myelin.
- Biophysical stimuli transiently increased phosphorylation of the integrin-associated tyrosine kinase Src within Schwann cells.
- Silencing this integrin signaling cascade blocked Src activation and prevented pressure-induced demyelination.
- Co-localization analysis indicated that Src is localized within Schwann cells.