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dc.contributor.authorPapale, Ligia Assumpção [UNIFESP]
dc.contributor.authorPaul, Ketema N.
dc.contributor.authorSawyer, Nikki T.
dc.contributor.authorManns, Joseph R.
dc.contributor.authorTufik, Sergio [UNIFESP]
dc.contributor.authorEscayg, Andrew
dc.identifier.citationJournal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 285, n. 22, p. 16553-16561, 2010.
dc.description.abstractVoltage-gated sodium channels (VGSCs) are responsible for the initiation and propagation of transient depolarizing currents and play a critical role in the electrical signaling between neurons. A null mutation in the VGSC gene SCN8A, which encodes the transmembrane protein Na(v)1.6, was identified previously in a human family. Heterozygous mutation carriers displayed a range of phenotypes, including ataxia, cognitive deficits, and emotional instability. A possible role for SCN8A was also proposed in studies examining the genetic basis of attempted suicide and bipolar disorder. in addition, mice with a Scn8a loss-of-function mutation (Scn8a(med-Tg/+)) show altered anxiety and depression-like phenotypes. Because psychiatric abnormalities are often associated with altered sleep and hormonal patterns, we evaluated heterozygous Scn8a(med-jo/+) mutants for alterations in sleep-wake architecture, diurnal corticosterone levels, and behavior. Compared with their wild-type littermates, Scn8a(med-jo/+) mutants experience more non-rapid eye movement (non-REM) sleep, a chronic impairment of REM sleep generation and quantity, and a lowered and flattened diurnal rhythm of corticosterone levels. No robust differences were observed between mutants and wild-type littermates in locomotor activity or in behavioral paradigms that evaluate anxiety or depression-like phenotypes; however, Scn8a(med-jo/+) mutants did show enhanced spatial memory. This study extends the spectrum of phenotypes associated with mutations in Scn8a and suggests a novel role for altered sodium channel function in human sleep disorders.en
dc.description.sponsorshipNational Institutes of Health
dc.publisherAmer Soc Biochemistry Molecular Biology Inc
dc.relation.ispartofJournal of Biological Chemistry
dc.rightsAcesso aberto
dc.titleDysfunction of the Scn8a Voltage-gated Sodium Channel Alters Sleep Architecture, Reduces Diurnal Corticosterone Levels, and Enhances Spatial Memoryen
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionEmory Univ
dc.contributor.institutionMorehouse Sch Med
dc.description.affiliationUniversidade Federal de São Paulo, Dept Psychobiol, BR-04024002 São Paulo, Brazil
dc.description.affiliationEmory Univ, Dept Human Genet, Atlanta, GA 30322 USA
dc.description.affiliationEmory Univ, Dept Psychol, Atlanta, GA 30322 USA
dc.description.affiliationMorehouse Sch Med, Dept Anat & Neurobiol, Atlanta, GA 30310 USA
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Dept Psychobiol, BR-04024002 São Paulo, Brazil
dc.description.sponsorshipIDNational Institutes of Health: NS046484
dc.description.sponsorshipIDNational Institutes of Health: NS065187
dc.description.sponsorshipIDNational Institutes of Health: NS060659
dc.description.sourceWeb of Science

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