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Search: WFRF:(Pérez Sala Dolores) > (2020-2023) > Astrocyte dysfuncti...

  • Canals, IsaacLund University,Lunds universitet,Stamceller, åldrande och neurodegeneration,Forskargrupper vid Lunds universitet,Glia och nervcellsbiologi,Stem Cells, Aging and Neurodegeneration,Lund University Research Groups,Glial and Neuronal Biology (author)

Astrocyte dysfunction and neuronal network hyperactivity in a CRISPR engineered pluripotent stem cell model of frontotemporal dementia

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • 2023

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:2d6e326f-e875-4f33-b766-e9952759037f
  • https://lup.lub.lu.se/record/2d6e326f-e875-4f33-b766-e9952759037fURI
  • https://doi.org/10.1093/braincomms/fcad158DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • Frontotemporal dementia (FTD) is the second most prevalent type of early-onset dementia and up to 40% of cases are familial forms. One of the genes mutated in patients is CHMP2B, which encodes a protein found in a complex important for maturation of late endosomes, an essential process for recycling membrane proteins through the endolysosomal system. Here, we have generated a CHMP2B-mutated human embryonic stem cell line using genome editing with the purpose to create a human in vitro FTD disease model. To date, most studies have focused on neuronal alterations; however, we present a new co-culture system in which neurons and astrocytes are independently generated from human embryonic stem cells and combined in co-cultures. With this approach, we have identified alterations in the endolysosomal system of FTD astrocytes, a higher capacity of astrocytes to uptake and respond to glutamate, and a neuronal network hyperactivity as well as excessive synchronization. Overall, our data indicates that astrocyte alterations precede neuronal impairments and could potentially trigger neuronal network changes, indicating the important and specific role of astrocytes in disease development.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Comella-Bolla, AndreaLund University,Lunds universitet,Stamceller, åldrande och neurodegeneration,Forskargrupper vid Lunds universitet,Stem Cells, Aging and Neurodegeneration,Lund University Research Groups(Swepub:lu)an6331co (author)
  • Cepeda-Prado, EfrainLund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Developmental and Regenerative Neurobiology,Lund University Research Groups(Swepub:lu)ef7187ce (author)
  • Avaliani, NataliaLund University,Lunds universitet,Experimentell Epilepsi,Forskargrupper vid Lunds universitet,Experimental Epilepsy Group,Lund University Research Groups(Swepub:lu)anal-nia (author)
  • Crowe, James ALund University,Lunds universitet,Glia och nervcellsbiologi,Forskargrupper vid Lunds universitet,Glial and Neuronal Biology,Lund University Research Groups(Swepub:lu)ja3743cr (author)
  • Oburoglu, LealLund University,Lunds universitet,Blodstamcellsutveckling,Forskargrupper vid Lunds universitet,Hematopoietic Stem Cell Development,Lund University Research Groups(Swepub:lu)le3434ob (author)
  • Bruzelius, AndreasLund University,Lunds universitet,Regenerativ neurofysiologi,Forskargrupper vid Lunds universitet,Regenerative Neurophysiology,Lund University Research Groups(Swepub:lu)an1575br (author)
  • King, NaomiLund University,Lunds universitet,Beteendevetenskapligt laboratorium,Forskargrupper vid Lunds universitet,Behavioural Neuroscience Laboratory,Lund University Research Groups(Swepub:lu)na5613ki (author)
  • Pajares, María ABiological Research Center (CIB), Madrid (author)
  • Pérez-Sala, DoloresBiological Research Center (CIB), Madrid (author)
  • Heuer, AndreasLund University,Lunds universitet,Beteendevetenskapligt laboratorium,Forskargrupper vid Lunds universitet,Behavioural Neuroscience Laboratory,Lund University Research Groups(Swepub:lu)med-ah4 (author)
  • Rylander Ottosson, DaniellaLund University,Lunds universitet,Regenerativ neurofysiologi,Forskargrupper vid Lunds universitet,Regenerative Neurophysiology,Lund University Research Groups(Swepub:lu)med-drr (author)
  • Soriano, JordiUniversity of Barcelona (author)
  • Ahlenius, HenrikLund University,Lunds universitet,Stamceller, åldrande och neurodegeneration,Forskargrupper vid Lunds universitet,Stem Cells, Aging and Neurodegeneration,Lund University Research Groups(Swepub:lu)neur-hah (author)
  • Stamceller, åldrande och neurodegenerationForskargrupper vid Lunds universitet (creator_code:org_t)

Related titles

  • In:Brain Communications5:3, s. 1-162632-1297

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