GLP-1 receptor agonist liraglutide has a neuroprotective effect on an aged rat model of Wolfram syndrome

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  • Kadri Seppa, University of Tartu
  • ,
  • Maarja Toots, University of Tartu
  • ,
  • Riin Reimets, University of Tartu
  • ,
  • Toomas Jagomäe, University of Tartu
  • ,
  • Tuuliki Koppel, University of Tartu
  • ,
  • Maia Pallase, University of Tartu
  • ,
  • Stine Hasselholt
  • Maiken Krogsbæk Mikkelsen
  • Jens Randel Nyengaard
  • Eero Vasar, University of Tartu
  • ,
  • Anton Terasmaa, University of Tartu
  • ,
  • Mario Plaas, University of Tartu

Wolfram syndrome (WS) is a rare neurodegenerative disorder that is mainly characterized by diabetes mellitus, optic nerve atrophy, deafness, and progressive brainstem degeneration. Treatment with GLP-1 receptor agonists has shown a promising anti-diabetic effect in WS treatment in both animal models and in human patients. Since previous research has tended to focus on investigation of the WS first symptom, diabetes mellitus, the aim of the present study was to examine liraglutide effect on WS-associated neurodegeneration. We took 9-month-old Wfs1 knock-out (KO) animals that already had developed glucose intolerance and treated them with liraglutide for 6 months. Our research results indicate that 6-month liraglutide treatment reduced neuroinflammation and ameliorated endoplasmic reticulum (ER) stress in the inferior olive of the aged WS rat model. Liraglutide treatment also protected retinal ganglion cells from cell death and optic nerve axons from degeneration. According to this, the results of the present study provide novel insight that GLP-1 receptor agonist liraglutide has a neuroprotective effect in the WS rat model.

Original languageEnglish
Article number15742
JournalScientific Reports
Volume9
Issue1
ISSN2045-2322
DOIs
Publication statusPublished - Dec 2019

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