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Nuclear distribution element-like 1 (NDEL1/NUDEL) is a mammalian homolog of the Aspergillus nidulans nuclear distribution molecule NudE. NDEL1 plays a critical role in neuronal migration, neurite outgrowth and neuronal positioning during brain development; however within the adult central nervous system, limited information is available regarding NDEL1 expression and functions. Here, the goal was to examine inducible NDEL1 expression in the adult mouse forebrain. Immunolabeling revealed NDEL1 within the forebrain, including the cortex and hippocampus, as well as the midbrain and hypothalamus. Expression was principally localized to perikarya. Using a combination of immunolabeling and RNA seq profiling, we detected a marked and long-lasting upregulation of NDEL1 expression within the hippocampus following a pilocarpine-evoked repetitive seizure paradigm. Chromatin immunoprecipitation (ChIP) analysis identified a cAMP response element-binding protein (CREB) binding site within the CpG island proximal to the NDEL1 gene, and in vivo transgenic repression of CREB led to a marked downregulation of seizure-evoked NDEL1 expression. Together these data indicate that NDEL1 is inducibly expressed in the adult nervous system, and that signaling via the CREB/CRE transcriptional pathway is likely involved. The role of NDEL1 in neuronal migration and neurite outgrowth during development raises the interesting prospect that inducible NDEL1 in the mature nervous system could contribute to the well-characterized structural and functional plasticity resulting from repetitive seizure activity. [ABSTRACT FROM AUTHOR]

Highlights: [•] This is the most detailed morphological documentation of Nde1 and Ndel1 both in vivo and in vitro. [•] This is the first histological study of Nde1 expression in the healthy human cortex. [•] We demonstrate the localization of Nde1 and Ndel1 in neurogenic regions of the adult mouse brain. [•] Overexpression of Nde1 and Ndel1 leads to the fate specification changes of neural stem cells. [ABSTRACT FROM AUTHOR]

Highlights: [•] NDEL1, DISC1 and p-ERK were involved in epileptogenesis of the adult hippocampus. [•] NDEL1 appeared tissue specificity in the hippocampus during the spontaneous seizure period after status epilepticus. [•] NDEL1 decreased in the CA3 and DG regions during the spontaneous seizure period. [•] NDEL1 increased in aberrant newborn blood vessels in the hippocampus during the spontaneous seizure period. [ABSTRACT FROM AUTHOR]