Molecular and behavioural abnormalities in the FUS-tg mice mimic frontotemporal lobar degeneration: Effects of old and new anti-inflammatory therapies

Johannes de Munter, Diana Babaevskaya, Erik Ch Wolters, Dmitrii Pavlov, Ekaterina Lysikova, Allan Kalueff, Anna Gorlova, Margarita Oplatchikova, Igor A. Pomytkin, Andrey Proshin, Aleksei Umriukhin, Klaus-Peter Lesch, Tatyana Strekalova*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Web of Science)


Genetic mutations in FUS, a DNA/RNA-binding protein, are associated with inherited forms of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). A novel transgenic FUS[1-359]-tg mouse line recapitulates core hallmarks of human ALS in the spinal cord, including neuroinflammation and neurodegeneration, ensuing muscle atrophy and paralysis, as well as brain pathomorphological signs of FTLD. However, a question whether FUS[1-359]-tg mouse displays behavioural and brain pro-inflammatory changes characteristic for the FTLD syndrome was not addressed. Here, we studied emotional, social and cognitive behaviours, brain markers of inflammation and plasticity of pre-symptomatic FUS[1-359]-tg male mice, a potential FTLD model. These animals displayed aberrant behaviours and altered brain expression of inflammatory markers and related pathways that are reminiscent to the FTLD-like syndrome. FTLD-related behavioural and molecular Journal of Cellular and Molecular Medicine features were studied in the pre-symptomatic FUS[1-359]-tg mice that received standard or new ALS treatments, which have been reported to counteract the ALS-like syndrome in the mutants. We used anti-ALS drug riluzole (8 mg/kg/d), or anti-inflammatory drug, a selective blocker of cyclooxygenase-2 (celecoxib, 30 mg/kg/d) for 3 weeks, or a single intracerebroventricular (i.c.v.) infusion of human stem cells (Neuro-Cells, 500 000-CD34(+)), which showed anti-inflammatory properties. Signs of elevated anxiety, depressive-like behaviour, cognitive deficits and abnormal social behaviour were less marked in FUS-tg-treated animals. Applied treatments have normalized protein expression of interleukin-1 beta (IL-1 beta) in the prefrontal cortex and the hippocampus, and of Iba-1 and GSK-3 beta in the hippocampus. Thus, the pre-symptomatic FUS[1-359]-tg mice demonstrate FTLD-like abnormalities that are attenuated by standard and new ALS treatments, including Neuro-Cell preparation.

Original languageEnglish
Pages (from-to)10251-10257
Number of pages7
JournalJournal of Cellular and Molecular Medicine
Issue number17
Publication statusPublished - Sep 2020


  • amyotrophic lateral sclerosis
  • animal model
  • celecoxib
  • emotionality and cognition
  • frontotemporal lobar degeneration
  • FUS[1-359]-tg mice
  • neuroinflammation
  • riluzole
  • stem cell therapy

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