Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Vascular regression precedes motor neuron loss in the FUS (1-359) ALS mouse model
Show others and affiliations
2019 (English)In: Disease Models and Mechanisms, ISSN 1754-8403, E-ISSN 1754-8411, Vol. 12, no 8, article id dmm040238Article in journal (Refereed) Published
Abstract [en]

Amyotrophic lateral sclerosis (ALS) presents a poorly understood pathogenesis. Evidence from patients and mutant SOD1 mouse models suggests vascular damage may precede or aggravate motor dysfunction in ALS. We have previously shown angiogenin (ANG) treatment enhances motor neuron survival, delays motor dysfunction and prevents vascular regression in the SOD1G93A ALS model. However, the existence of vascular defects at different stages of disease progression remains to be established in other ALS models. Here, we assessed vascular integrity in vivo throughout different disease stages, and investigated whether ANG treatment reverses vascular regression and prolongs motor neuron survival in the FUS (1-359) mouse model of ALS. Lumbar spinal cord tissue was collected from FUS (1-359) and non-transgenic control mice at postnatal day (P)50, P90 and P120. We found a significant decrease in vascular network density in lumbar spinal cords from FUS (1-359) mice by day 90, at which point motor neuron numbers were unaffected. ANG treatment did not affect survival or counter vascular regression. Endogenous Ang1 and Vegf expression were unchanged at P50 and P90; however, we found a significant decrease in miRNA 126 at P50, indicating vascular integrity in FUS mice may be compromised via an alternative pathway. Our study demonstrates that vascular regression occurs before motor neuron degeneration in FUS (1-359) mice, and highlights that heterogeneity in responses to novel ALS therapeutics can already be detected in preclinical mouse models of ALS.

Place, publisher, year, edition, pages
Company of Biologists Ltd , 2019. Vol. 12, no 8, article id dmm040238
Keywords [en]
Amyotrophic lateral sclerosis, Angiogenin, FUS, Motoneuron, Vascular defects
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:kth:diva-262407DOI: 10.1242/dmm.040238ISI: 000484375400010Scopus ID: 2-s2.0-85071354116OAI: oai:DiVA.org:kth-262407DiVA, id: diva2:1366645
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20191030

Available from: 2019-10-30 Created: 2019-10-30 Last updated: 2019-11-06Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textScopus

Authority records BETA

Lewandowski, Sebastian

Search in DiVA

By author/editor
Lewandowski, Sebastian
By organisation
Affinity ProteomicsScience for Life Laboratory, SciLifeLab
In the same journal
Disease Models and Mechanisms
Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 84 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf