title: Developmental Alcohol Exposure Impairs Activity-Dependent S-Nitrosylation of NDEL1 for Neuronal Maturation.
abstract: Neuronal nitric oxide synthase is involved in diverse signaling cascades that regulate neuronal development and functions via S-Nitrosylation-mediated mechanism or the soluble guanylate cyclase (sGC)/cyclic guanosine monophosphate (cGMP) pathway activated by nitric oxide. Although it has been studied extensively in vitro and in invertebrate animals, effects on mammalian brain development and underlying mechanisms remain poorly understood. Here we report that genetic deletion of "Nos1" disrupts dendritic development, whereas pharmacological inhibition of the sGC/cGMP pathway does not alter dendritic growth during cerebral cortex development. Instead, nuclear distribution element-like (NDEL1), a protein that regulates dendritic development, is specifically S-nitrosylated at cysteine 203, thereby accelerating dendritic arborization. This post-translational modification is enhanced by N-methyl-D-aspartate receptor-mediated neuronal activity, the main regulator of dendritic formation. Notably, we found that disruption of S-Nitrosylation of NDEL1 mediates impaired dendritic maturation caused by developmental alcohol exposure, a model of developmental brain abnormalities resulting from maternal alcohol use. These results highlight S-Nitrosylation as a key activity-dependent mechanism underlying neonatal brain maturation and suggest that reduction of S-Nitrosylation of NDEL1 acts as a pathological factor mediating neurodevelopmental abnormalities caused by maternal alcohol exposure.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.|Department of Biological Psychiatry and Neuroscience, Dokkyo Medical University School of Medicine, Shimotsuga-gun, Tochigi 321-0293, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Saito
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Taniguchi
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Sun-Hong
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Balakrishnan
authors.initials: B
authors.lastname: Selvakumar
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Perez
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Ballinger
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: James
authors.initials: J
authors.lastname: Sabra
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Mariama
authors.initials: M
authors.lastname: Jallow
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Yan
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Koki
authors.initials: K
authors.lastname: Ito
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Shreenath
authors.initials: S
authors.lastname: Rajendran
authors.affiliation: Department of Genetic Disease Research, Osaka City University Graduate School of Medicine, Abeno, Osaka 545-8585, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Hirotsune
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Wynshaw-Boris
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Solomon H
authors.initials: SH
authors.lastname: Snyder
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.|Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Akira
authors.initials: A
authors.lastname: Sawa
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kamiya
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D052248:Nitric Oxide Synthase Type I / Q000172:deficiency / Q000235:genetics; D017397:Prefrontal Cortex / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D002352:Carrier Proteins; C421108:NDEL1 protein, human; C486015:Ndel1 protein, mouse; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse
keywords: NDEL1; S-Nitrosylation; dendritic development; fetal alcohol spectrum disorder; neuronal activity