Nuclear distribution element-like 1 is associated with dentate gyrus remodeling after status epilepticus in a pilocarpine-induced mouse model.

Abstract

Structural remodeling of the dentate gyrus is a hallmark of temporal lobe epilepsy (TLE), yet the underlying molecular mechanisms remain incompletely understood. Nuclear distribution element-like 1 (Ndel1), a cytoskeleton-associated protein involved in neuronal migration and dendritic development, has not been characterized in dentate gyrus remodeling during epileptogenesis. Here, we investigated region- and cell-type-specific alterations in Ndel1 expression in a pilocarpine-induced mouse model of TLE and examined the effects of adeno-associated virus (AAV)-mediated Ndel1 expression on structural remodeling. Immunofluorescence was used to define Ndel1 localization across neural stem cells, granule lineage cells, mature neurons, and astrocytes, and dendritic architecture was assessed using Golgi staining and Sholl analysis. Total hippocampal Ndel1 expression increased after status epilepticus, whereas Ndel1-positive cells decreased selectively in the subgranular zone but increased among granule lineage cells in the hilus. Ndel1 was preferentially expressed in BLBP-positive neural stem cells and mature neurons, but not in neuroblasts. Activated astrocytic processes exhibited increased spatial association with Ndel1-positive cells during early remodeling. Ndel1 overexpression was associated with partial normalization of neuronal marker distribution, increased dendritic spine density, and reduced dendritic branching complexity. These findings suggest that Ndel1 is associated with region- and lineage-specific structural remodeling in the dentate gyrus during epileptogenesis.