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Unexpected Transcriptional Programs Contribute to Hippocampal Memory Deficits and Neuronal Stunting after Early-Life Adversity.
Bolton, Jessica L; Schulmann, Anton; Garcia-Curran, Megan M; Regev, Limor; Chen, Yuncai; Kamei, Noriko; Shao, Manlin; Singh-Taylor, Akanksha; Jiang, Shan; Noam, Yoav; Molet, Jenny; Mortazavi, Ali; Baram, Tallie Z.
Afiliación
  • Bolton JL; Department of Pediatrics, University of California, Irvine, Irvine, CA 92697-4475, USA; Department of Anatomy/Neurobiology, University of California, Irvine, Irvine, CA 92697-4475, USA.
  • Schulmann A; Department of Pediatrics, University of California, Irvine, Irvine, CA 92697-4475, USA; Department of Anatomy/Neurobiology, University of California, Irvine, Irvine, CA 92697-4475, USA.
  • Garcia-Curran MM; Department of Pediatrics, University of California, Irvine, Irvine, CA 92697-4475, USA; Department of Anatomy/Neurobiology, University of California, Irvine, Irvine, CA 92697-4475, USA.
  • Regev L; Department of Pediatrics, University of California, Irvine, Irvine, CA 92697-4475, USA; Department of Anatomy/Neurobiology, University of California, Irvine, Irvine, CA 92697-4475, USA.
  • Chen Y; Department of Pediatrics, University of California, Irvine, Irvine, CA 92697-4475, USA; Department of Anatomy/Neurobiology, University of California, Irvine, Irvine, CA 92697-4475, USA.
  • Kamei N; Department of Pediatrics, University of California, Irvine, Irvine, CA 92697-4475, USA; Department of Anatomy/Neurobiology, University of California, Irvine, Irvine, CA 92697-4475, USA.
  • Shao M; Department of Pediatrics, University of California, Irvine, Irvine, CA 92697-4475, USA; Department of Anatomy/Neurobiology, University of California, Irvine, Irvine, CA 92697-4475, USA.
  • Singh-Taylor A; Department of Pediatrics, University of California, Irvine, Irvine, CA 92697-4475, USA; Department of Anatomy/Neurobiology, University of California, Irvine, Irvine, CA 92697-4475, USA.
  • Jiang S; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697-4475, USA.
  • Noam Y; Department of Pediatrics, University of California, Irvine, Irvine, CA 92697-4475, USA; Department of Anatomy/Neurobiology, University of California, Irvine, Irvine, CA 92697-4475, USA.
  • Molet J; Department of Pediatrics, University of California, Irvine, Irvine, CA 92697-4475, USA; Department of Anatomy/Neurobiology, University of California, Irvine, Irvine, CA 92697-4475, USA.
  • Mortazavi A; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697-4475, USA.
  • Baram TZ; Department of Pediatrics, University of California, Irvine, Irvine, CA 92697-4475, USA; Department of Anatomy/Neurobiology, University of California, Irvine, Irvine, CA 92697-4475, USA; Department of Neurology, University of California, Irvine, Irvine, CA 92697-4475, USA. Electronic address: tallie@
Cell Rep ; 33(11): 108511, 2020 12 15.
Article en En | MEDLINE | ID: mdl-33326786
Early-life adversity (ELA) is associated with lifelong memory deficits, yet the responsible mechanisms remain unclear. We impose ELA by rearing rat pups in simulated poverty, assess hippocampal memory, and probe changes in gene expression, their transcriptional regulation, and the consequent changes in hippocampal neuronal structure. ELA rats have poor hippocampal memory and stunted hippocampal pyramidal neurons associated with ~140 differentially expressed genes. Upstream regulators of the altered genes include glucocorticoid receptor and, unexpectedly, the transcription factor neuron-restrictive silencer factor (NRSF/REST). NRSF contributes critically to the memory deficits because blocking its function transiently following ELA rescues spatial memory and restores the dendritic arborization of hippocampal pyramidal neurons in ELA rats. Blocking NRSF function in vitro augments dendritic complexity of developing hippocampal neurons, suggesting that NRSF represses genes involved in neuronal maturation. These findings establish important, surprising contributions of NRSF to ELA-induced transcriptional programming that disrupts hippocampal maturation and memory function.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Hipocampo / Trastornos de la Memoria / Neuronas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Hipocampo / Trastornos de la Memoria / Neuronas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos