Atomic force microscopy study of ECM‐integrin modulation of neuroplasticity in the hippocampal dentate granule cells in epilepsy

Integrins as membrane receptors on neurons play a key role in the development of neuroplasticity in the brain. Integrin recruitment and relocalization, and extracellular matrix protein (ECM)‐integrin attachments have been reported to dynamically change their position during cell spreading and migration. In this study, we hypothesized that ECM‐integrin bond formation and cell elasticity (remodeling) are altered in epilepsy. We tested this premise in adult mouse hippocampal dentate granule cells (DGCs) in stage 5 hippocampal kindling model of epilepsy by using nanoscale atomic force microscopy (AFM) and immunocytochemistry. The α5β1‐ integrin staining intensity in DGCs from epilepsy mice was at least 10% stronger than in control. In AFM study, the unbinding force (25.6 ± 0.2 pN) and binding probability between ECM protein FN‐coated AFM probe and membrane integrins in epilepsy DGCs were 49% and 18% lower than control, respectively (p<0.05, n=10). FN‐integrin binding probability was significantly reduced by anti‐α5β1 integrin in control. Moreover, the cell elasticity, representing changes in cytoskeletal reorganization, was 66% increased in epilepsy. These results indicate that FN‐adhesive activities are functional specific and primarily bound to α5β1 integrin. Therefore, it is likely that dynamic changes in plasticity properties of DGCs contribute to epileptogenesis.