Status epilepticus stimulates NDEL1 expression via the CREB/CRE pathway in the adult mouse brain.
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.
Department of Pharmaceutical Science & Technology, Catholic University of Daegu, Gyeongbuk, Republic of Korea.
Yun-Sik
YS
Choi
Center for Cognition and Sociality, Institute for Basic Science, Seoul, Republic of Korea.
Boyoung
B
Lee
Department of Neuroscience, Ohio State University, Columbus, OH, USA.
Katelin F
KF
Hansen
Department of Neuroscience, Ohio State University, Columbus, OH, USA.
Sydney
S
Aten
Department of Neuroscience, Ohio State University, Columbus, OH, USA.
Paul
P
Horning
Division of Pharmacology, Ohio State University, Columbus, OH, USA.
Kelin L
KL
Wheaton
Oregon Health and Science University, Portland, OR, USA.
Soren
S
Impey
Division of Pharmacology, Ohio State University, Columbus, OH, USA.
Kari R
KR
Hoyt
Department of Neuroscience, Ohio State University, Columbus, OH, USA. Electronic address: obrietan.1@osu.edu.
Karl
K
Obrietan
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010862:Pilocarpine; D016548:Prosencephalon / Q000378:metabolism* / Q000473:pathology; D013226:Status Epilepticus / Q000378:metabolism* / Q000473:pathology
D002352:Carrier Proteins; D017362:Cyclic AMP Response Element-Binding Protein; C421108:NDEL1 protein, human; C486015:Ndel1 protein, mouse; C485184:enhanced green fluorescent protein; D010862:Pilocarpine; D049452:Green Fluorescent Proteins
CRE; CREB; NDEL1; hippocampus; seizure