Status epilepticus stimulates NDEL1 expression via the CREB/CRE pathway in the adult mouse brain

Yun Sik Choi, Boyoung Lee, Katelin F. Hansen, Sydney Aten, Paul Horning, Kelin L. Wheaton, Soren Impey, Kari R. Hoyt, Karl Obrietan

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalNeuroscience
Volume331
DOIs
StatePublished - Sep 7 2016

Fingerprint

Cyclic AMP Response Element-Binding Protein
Status Epilepticus
Seizures
Prosencephalon
Nervous System
Hippocampus
Brain
Aspergillus nidulans
CpG Islands
Pilocarpine
Chromatin Immunoprecipitation
Mesencephalon
Protein Binding
Hypothalamus
Up-Regulation
Down-Regulation
Central Nervous System
Binding Sites
RNA
Genes

Keywords

  • CRE
  • CREB
  • hippocampus
  • NDEL1
  • seizure

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Choi, Y. S., Lee, B., Hansen, K. F., Aten, S., Horning, P., Wheaton, K. L., ... Obrietan, K. (2016). Status epilepticus stimulates NDEL1 expression via the CREB/CRE pathway in the adult mouse brain. Neuroscience, 331, 1-12. https://doi.org/10.1016/j.neuroscience.2016.06.010

Status epilepticus stimulates NDEL1 expression via the CREB/CRE pathway in the adult mouse brain. / Choi, Yun Sik; Lee, Boyoung; Hansen, Katelin F.; Aten, Sydney; Horning, Paul; Wheaton, Kelin L.; Impey, Soren; Hoyt, Kari R.; Obrietan, Karl.

In: Neuroscience, Vol. 331, 07.09.2016, p. 1-12.

Research output: Contribution to journalArticle

Choi, YS, Lee, B, Hansen, KF, Aten, S, Horning, P, Wheaton, KL, Impey, S, Hoyt, KR & Obrietan, K 2016, 'Status epilepticus stimulates NDEL1 expression via the CREB/CRE pathway in the adult mouse brain', Neuroscience, vol. 331, pp. 1-12. https://doi.org/10.1016/j.neuroscience.2016.06.010
Choi, Yun Sik ; Lee, Boyoung ; Hansen, Katelin F. ; Aten, Sydney ; Horning, Paul ; Wheaton, Kelin L. ; Impey, Soren ; Hoyt, Kari R. ; Obrietan, Karl. / Status epilepticus stimulates NDEL1 expression via the CREB/CRE pathway in the adult mouse brain. In: Neuroscience. 2016 ; Vol. 331. pp. 1-12.
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