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Mutation of neuron-specific chromatin remodeling subunit BAF53b: rescue of plasticity and memory by manipulating actin remodeling.
Vogel Ciernia, Annie; Kramár, Enikö A; Matheos, Dina P; Havekes, Robbert; Hemstedt, Thekla J; Magnan, Christophe N; Sakata, Keith; Tran, Ashley; Azzawi, Soraya; Lopez, Alberto; Dang, Richard; Wang, Weisheng; Trieu, Brian; Tong, Joyce; Barrett, Ruth M; Post, Rebecca J; Baldi, Pierre; Abel, Ted; Lynch, Gary; Wood, Marcelo A.
Afiliação
  • Vogel Ciernia A; Department of Medical Microbiology and Immunology, University of California, Davis, California 95656, USA.
  • Kramár EA; Department of Neurobiology and Behavior, University of California, Irvine, California 92697, USA.
  • Matheos DP; Center for the Neurobiology of Learning and Memory, Irvine, California, USA.
  • Havekes R; Department of Neurobiology and Behavior, University of California, Irvine, California 92697, USA.
  • Hemstedt TJ; Center for the Neurobiology of Learning and Memory, Irvine, California, USA.
  • Magnan CN; Groningen Institute for Evolutionary Life Sciences (GELIFES), University of Groningen, Groningen 9712, The Netherlands.
  • Sakata K; Department of Neurobiology and Behavior, University of California, Irvine, California 92697, USA.
  • Tran A; Center for the Neurobiology of Learning and Memory, Irvine, California, USA.
  • Azzawi S; Department of Computer Science, University of California, Irvine, California 92697, USA.
  • Lopez A; Institute for Genomics and Bioinformatics, University of California, Irvine, California 92697, USA.
  • Dang R; Department of Neurobiology and Behavior, University of California, Irvine, California 92697, USA.
  • Wang W; Center for the Neurobiology of Learning and Memory, Irvine, California, USA.
  • Trieu B; Department of Neurobiology and Behavior, University of California, Irvine, California 92697, USA.
  • Tong J; Center for the Neurobiology of Learning and Memory, Irvine, California, USA.
  • Barrett RM; Department of Neurobiology and Behavior, University of California, Irvine, California 92697, USA.
  • Post RJ; Center for the Neurobiology of Learning and Memory, Irvine, California, USA.
  • Baldi P; Department of Neurobiology and Behavior, University of California, Irvine, California 92697, USA.
  • Abel T; Center for the Neurobiology of Learning and Memory, Irvine, California, USA.
  • Lynch G; Department of Neurobiology and Behavior, University of California, Irvine, California 92697, USA.
  • Wood MA; Center for the Neurobiology of Learning and Memory, Irvine, California, USA.
Learn Mem ; 24(5): 199-209, 2017 05.
Article em En | MEDLINE | ID: mdl-28416631
Recent human exome-sequencing studies have implicated polymorphic Brg1-associated factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in several intellectual disabilities and cognitive disorders, including autism. However, it remains unclear how mutations in BAF complexes result in impaired cognitive function. Post-mitotic neurons express a neuron-specific assembly, nBAF, characterized by the neuron-specific subunit BAF53b. Subdomain 2 of BAF53b is essential for the differentiation of neuronal precursor cells into neurons. We generated transgenic mice lacking subdomain 2 of Baf53b (BAF53bΔSB2). Long-term synaptic potentiation (LTP) and long-term memory, both of which are associated with phosphorylation of the actin severing protein cofilin, were assessed in these animals. A phosphorylation mimic of cofilin was stereotaxically delivered into the hippocampus of BAF53bΔSB2 mice in an effort to rescue LTP and memory. BAF53bΔSB2 mutant mice show impairments in phosphorylation of synaptic cofilin, LTP, and memory. Both the synaptic plasticity and memory deficits are rescued by overexpression of a phosphorylation mimetic of cofilin. Baseline physiology and behavior were not affected by the mutation or the experimental treatment. This study suggests a potential link between nBAF function, actin cytoskeletal remodeling at the dendritic spine, and memory formation. This work shows that a targeted manipulation of synaptic function can rescue adult plasticity and memory deficits caused by manipulations of nBAF, and thereby provides potential novel avenues for therapeutic development for multiple intellectual disability disorders.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fosfopiruvato Hidratase / Proteínas Cromossômicas não Histona / Montagem e Desmontagem da Cromatina / Memória / Mutação / Plasticidade Neuronal Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fosfopiruvato Hidratase / Proteínas Cromossômicas não Histona / Montagem e Desmontagem da Cromatina / Memória / Mutação / Plasticidade Neuronal Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2017 Tipo de documento: Article