Dysfunction of the Scn8a Voltage-gated Sodium Channel Alters Sleep Architecture, Reduces Diurnal Corticosterone Levels, and Enhances Spatial Memory

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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.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionEmory Univ
dc.contributor.institutionMorehouse Sch Med
dc.date.accessioned2016-01-24T13:59:42Z
dc.date.available2016-01-24T13:59:42Z
dc.date.issued2010-05-28
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.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.sourceWeb of Science
dc.description.sponsorshipNational Institutes of Health
dc.description.sponsorshipIDNational Institutes of Health: NS046484
dc.description.sponsorshipIDNational Institutes of Health: NS065187
dc.description.sponsorshipIDNational Institutes of Health: NS060659
dc.format.extent16553-16561
dc.identifierhttp://dx.doi.org/10.1074/jbc.M109.090084
dc.identifier.citationJournal of Biological Chemistry. Bethesda: Amer Soc Biochemistry Molecular Biology Inc, v. 285, n. 22, p. 16553-16561, 2010.
dc.identifier.doi10.1074/jbc.M109.090084
dc.identifier.issn0021-9258
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/32553
dc.identifier.wosWOS:000277982600018
dc.language.isoeng
dc.publisherAmer Soc Biochemistry Molecular Biology Inc
dc.relation.ispartofJournal of Biological Chemistry
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleDysfunction of the Scn8a Voltage-gated Sodium Channel Alters Sleep Architecture, Reduces Diurnal Corticosterone Levels, and Enhances Spatial Memoryen
dc.typeinfo:eu-repo/semantics/article
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