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  • Gabery, SanazLund University,Lunds universitet,Translationell neuroendokrinologi,Forskargrupper vid Lunds universitet,Translational Neuroendocrinology,Lund University Research Groups (författare)

Early white matter pathology in the fornix of the limbic system in Huntington disease

  • Artikel/kapitelEngelska2021

Förlag, utgivningsår, omfång ...

  • 2021-08-26
  • Springer Science and Business Media LLC,2021

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:b10b758f-af5a-4e62-915f-69c7cb3ad76f
  • https://lup.lub.lu.se/record/b10b758f-af5a-4e62-915f-69c7cb3ad76fURI
  • https://doi.org/10.1007/s00401-021-02362-8DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:art swepub-publicationtype
  • Ämneskategori:ref swepub-contenttype

Anmärkningar

  • Huntington disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin (HTT) gene. The typical motor symptoms have been associated with basal ganglia pathology. However, psychiatric and cognitive symptoms often precede the motor component and may be due to changes in the limbic system. Recent work has indicated pathology in the hypothalamus in HD but other parts of the limbic system have not been extensively studied. Emerging evidence suggests that changes in HD also include white matter pathology. Here we investigated if the main white matter tract of the limbic system, the fornix, is affected in HD. We demonstrate that the fornix is 34% smaller already in prodromal HD and 41% smaller in manifest HD compared to controls using volumetric analyses of MRI of the IMAGE-HD study. In post-mortem fornix tissue from HD cases, we confirm the smaller fornix volume in HD which is accompanied by signs of myelin breakdown and reduced levels of the transcription factor myelin regulating factor but detect no loss of oligodendrocytes. Further analyses using RNA-sequencing demonstrate downregulation of oligodendrocyte identity markers in the fornix of HD cases. Analysis of differentially expressed genes based on transcription-factor/target-gene interactions also revealed enrichment for binding sites of SUZ12 and EZH2, components of the Polycomb Repressive Complex 2, as well as RE1 Regulation Transcription Factor. Taken together, our data show that there is early white matter pathology of the fornix in the limbic system in HD likely due to a combination of reduction in oligodendrocyte genes and myelin break down.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Kwa, Jing EugeneAgency for Science, Technology and Research (A*STAR) (författare)
  • Cheong, Rachel Y.Lund University,Lunds universitet,Brain Repair and Imaging in Neural Systems (BRAINS),Forskargrupper vid Lunds universitet,Translationell neuroendokrinologi,Lund University Research Groups,Translational Neuroendocrinology(Swepub:lu)med-rco (författare)
  • Baldo, BarbaraLund University,Lunds universitet,Translationell neuroendokrinologi,Forskargrupper vid Lunds universitet,Translational Neuroendocrinology,Lund University Research Groups,Evotec AG(Swepub:lu)med-bbo (författare)
  • Ferrari Bardile, CostanzaUniversity of British Columbia,Agency for Science, Technology and Research (A*STAR) (författare)
  • Tan, BrendanMonash University (författare)
  • McLean, CatrionaAlfred Hospital (författare)
  • Georgiou-Karistianis, NellieMonash University (författare)
  • Poudel, Govinda R.Monash University (författare)
  • Halliday, GlendaUniversity of Sydney (författare)
  • Pouladi, Mahmoud A.University of British Columbia,Agency for Science, Technology and Research (A*STAR),National University of Singapore (författare)
  • Petersén, ÅsaLund University,Lunds universitet,Translationell neuroendokrinologi,Forskargrupper vid Lunds universitet,Psykiatri, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Translational Neuroendocrinology,Lund University Research Groups,Psychiatry (Lund),Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)mphy-apn (författare)
  • Translationell neuroendokrinologiForskargrupper vid Lunds universitet (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Acta Neuropathologica: Springer Science and Business Media LLC142:5, s. 791-8060001-63221432-0533

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