Atomic force microscopy investigations of fibronectin and α5β1-integrin signaling in neuroplasticity and seizure susceptibility in experimental epilepsy

Epilepsy Research
Xin WuDoodipala Samba Reddy

Abstract

Extracellular matrix protein-integrin interaction on neurons plays an important role in the development of neuroplasticity in the brain. However, the role of fibronectin-integrin signaling in epilepsy is elusive. Here, we examined the functional role of fibronectin-integrin signaling by utilizing a combination approach involving atomic force microscopy (AFM), immunocytochemistry, and pharmacology in epileptic mouse dentate gyrus granule cells (DGGCs). There was marked increase in the fibronectin receptor α5β1-integrin staining intensity in DGGCs in epileptic mice. In the AFM study, the unbinding force and binding probability between the fibronectin-coated AFM probe and the membrane integrins were significantly reduced; while the cell stiffness was strikingly increased in epileptic DGGCs. Pretreatment with α5β1-integrin monoclonal antibody partially reversed this membrane dysfunction. In patch-clamp recordings, fibronectin significantly inhibited GABA current, while RGD, which is known to disrupt fibronectin-integrin-dependent cell adhesive events, strikingly enhanced GABA tonic currents in DGGCs in hippocampal slices. The α5β1-integrin antibody significantly reduced 4-aminopyridine-induced epileptiform discharges in brain slice...Continue Reading

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