Cristin-prosjekt-ID: 543194
Sist endret: 13. august 2018 09:58
Cristin-prosjekt-ID: 543194
Sist endret: 13. august 2018 09:58
Prosjekt

Noncoding RNA in synaptic plasticity and disease

prosjektleder

Karin Wibrand
ved Universitetet i Bergen

prosjekteier / koordinerende forskningsansvarlig enhet

  • Universitetet i Bergen

Finansiering

  • TotalbudsjettNOK 3.300.000
  • Bergens forskningsstiftelse

Klassifisering

Vitenskapsdisipliner

Molekylærbiologi

Emneord

Neurovitenskap / nevrovitenskap

Kategorier

Prosjektkategori

  • Grunnforskning

Kontaktinformasjon

Sted
Karin Wibrand

Tidsramme

Avsluttet
Start: 31. august 2012 Slutt: 31. august 2015

Beskrivelse Beskrivelse

Tittel

Noncoding RNA in synaptic plasticity and disease

Vitenskapelig sammendrag

In this project financed by Bergen Medical Research Foundation we explored the involvment of long noncoding regulatory RNA in synaptic platicity. 

Long-term potentiation (LTP) of synaptic transmission is recognized as a cellular mechanism for learning and memory storage. Although de novo gene transcription is known to be required in the formation of stable LTP, the molecular mechanisms underlying synaptic plasticity remain elusive. Noncoding RNAs have emerged as major regulatory molecules that are abundantly and specifically expressed in the mammalian brain. By combining RNA-seq analysis with LTP induction in the dentate gyrus of live rats, we provide the first global transcriptomic analysis of synaptic plasticity in the adult brain. Expression profiles of mRNAs and long noncoding RNAs (lncRNAs) were obtained at 30 min, 2 and 5 h after high-frequency stimulation of the perforant pathway. The temporal analysis revealed dynamic expression profiles of lncRNAs with many positively, and highly, correlated to protein-coding genes with known roles in synaptic plasticity, suggesting their possible involvement in LTP. In light of observations suggesting a role for retrotransposons in brain function, we examined the expression of various classes of repeat elements. Our analysis identifies dynamic regulation of LINE1 and SINE retrotransposons, and extensive regulation of tRNA. These experiments reveal a hitherto unknown complexity of gene expression in long-term synaptic plasticity involving the dynamic regulation of lncRNAs and repeat elements. These findings provide a broader foundation for elucidating the transcriptional and epigenetic regulation of synaptic plasticity in both the healthy brain and in neurodegenerative and neuropsychiatric disorders.

Keywords: long noncoding RNA (lncRNA), LTP (long term potentiation), retrotransposons, repeat elements, rat brain, time-series data, synaptic plasticity (LTP/LTD)

prosjektdeltakere

prosjektleder

Karin Wibrand

  • Tilknyttet:
    Prosjektleder
    ved Universitetet i Bergen

Clive R. Bramham

  • Tilknyttet:
    Prosjektdeltaker
    ved Universitetet i Bergen

Marcel E. Dinger

  • Tilknyttet:
    Prosjektdeltaker
    ved Garvan Institute of Medical Research
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Resultater Resultater

Widespread promoter methylation of synaptic plasticity genes in long-term potentiation in the adult brain in vivo.

Maag, Jesper L.V.; Kaczorowski, Dominik C.; Panja, Debabrata; Peters, Timothy J.; Bramham, Clive R.; Wibrand, Karin; Dinger, Marcel E.. 2017, BMC Genomics. GARVAN, UIBVitenskapelig artikkel

Corrigendum to Dynamic expression of long noncoding RNAs and repeat elements in synaptic plasticity [Front. Neurosci. (2015), 9:351. doi: 10.3389/fnins.2015.00351].

Maag, Jesper L.V.; Panja, Debabrata; Sporild, Ida; Patil, Sudarshan; Kaczorowski, Dominik C.; Bramham, Clive R.; Dinger, Marcel E.; Wibrand, Karin. 2016, Frontiers in Neuroscience. GARVAN, UNSW, UIBErrata

Dynamic expression of long noncoding RNAs and repeat elements in synaptic plasticity.

Maag, Jesper L.V.; Panja, Debabrata; Sporild, Ida; Patil, Sudarshan; Kaczorowski, Dominik C.; Bramham, Clive R.; Dinger, Marcel E.; Wibrand, Karin. 2015, Frontiers in Neuroscience. GARVAN, UNSW, UIBVitenskapelig artikkel

Characterization of two predicted long non-coding RNAs in long-term synaptic plasticity in rat hippocampus.

Sporild, Ida. 2014, UIBMastergradsoppgave
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