Please use this identifier to cite or link to this item: http://hdl.handle.net/10995/101492
Title: Molecular and behavioural abnormalities in the FUS-tg mice mimic frontotemporal lobar degeneration: Effects of old and new anti-inflammatory therapies
Authors: de, Munter, J.
Babaevskaya, D.
Wolters, E. C.
Pavlov, D.
Lysikova, E.
V. , Kalueff, A.
Gorlova, A.
Oplatchikova, M.
Pomytkin, I. A.
Proshin, A.
Umriukhin, A.
Lesch, K. -P.
Strekalova, T.
Issue Date: 2020
Publisher: Blackwell Publishing Inc.
Citation: Molecular and behavioural abnormalities in the FUS-tg mice mimic frontotemporal lobar degeneration: Effects of old and new anti-inflammatory therapies / J. de Munter, D. Babaevskaya, E. C. Wolters, et al. — DOI 10.1111/jcmm.15628 // Journal of Cellular and Molecular Medicine. — 2020. — Vol. 24. — Iss. 17. — P. 10251-10257.
Abstract: 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-1β (IL-1β) in the prefrontal cortex and the hippocampus, and of Iba-1 and GSK-3β 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. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd
Keywords: AMYOTROPHIC LATERAL SCLEROSIS
ANIMAL MODEL
CELECOXIB
EMOTIONALITY AND COGNITION
FRONTOTEMPORAL LOBAR DEGENERATION
FUS[1-359]-TG MICE
NEUROINFLAMMATION
RILUZOLE
STEM CELL THERAPY
BIOLOGICAL MARKER
CALCIUM BINDING PROTEIN
CELECOXIB
CYCLOOXYGENASE 1
GELATINASE B
GLYCOGEN SYNTHASE KINASE 3ALPHA
GLYCOGEN SYNTHASE KINASE 3BETA
INTERLEUKIN 1BETA
IONIZED CALCIUM BINDING ADAPTOR MOLECULE 1
MOLECULAR MARKER
RILUZOLE
RNA BINDING PROTEIN FUS
TISSUE INHIBITOR OF METALLOPROTEINASE 1
TUMOR NECROSIS FACTOR
UNCLASSIFIED DRUG
ANTIINFLAMMATORY AGENT
CYCLOOXYGENASE 2
FUS PROTEIN, MOUSE
GLYCOGEN SYNTHASE KINASE 3BETA
INTERLEUKIN 1BETA
RNA BINDING PROTEIN FUS
ABNORMAL BEHAVIOR
ADULT
AMYOTROPHIC LATERAL SCLEROSIS
ANIMAL EXPERIMENT
ANIMAL MODEL
ANIMAL TISSUE
ANTIINFLAMMATORY ACTIVITY
ANXIETY
ARTICLE
CAGE TEST
COGNITION
COGNITIVE DEFECT
CONTROLLED STUDY
DEPRESSION
ELEVATED PLUS MAZE TEST
EMOTION
EXPERIMENTAL NEUROINFLAMMATION
FRONTOTEMPORAL DEMENTIA
GENE MUTATION
GENOTYPE
HIPPOCAMPUS
HOME-CAGE ACTIVITY TEST
INFLAMMATION
INTRACEREBROVENTRICULAR DRUG ADMINISTRATION
LOCOMOTION
MALE
MARBLE BURYING TEST
MOUSE
NERVE DEGENERATION
NONHUMAN
OPEN FIELD TEST
PLASTICITY
PREFRONTAL CORTEX
PROTEIN EXPRESSION
REAL TIME POLYMERASE CHAIN REACTION
RESIDENT-INTRUDER TEST
RNA ISOLATION
SOCIAL BEHAVIOR
STEM CELL
SUCROSE PREFERENCE TEST
TAIL SUSPENSION TEST
TRANSGENIC MOUSE
WESTERN BLOTTING
ANIMAL
ANIMAL BEHAVIOR
BRAIN
DRUG EFFECT
FRONTOTEMPORAL DEMENTIA
INFLAMMATION
METABOLISM
MUTATION
NERVE CELL
SPINAL CORD
AMYOTROPHIC LATERAL SCLEROSIS
ANIMALS
ANTI-INFLAMMATORY AGENTS
BEHAVIOR, ANIMAL
BRAIN
CYCLOOXYGENASE 2
FRONTOTEMPORAL LOBAR DEGENERATION
GLYCOGEN SYNTHASE KINASE 3 BETA
INFLAMMATION
INTERLEUKIN-1BETA
MALE
MICE
MUTATION
NEURONS
RNA-BINDING PROTEIN FUS
SOCIAL BEHAVIOR
SPINAL CORD
URI: http://hdl.handle.net/10995/101492
Access: info:eu-repo/semantics/openAccess
SCOPUS ID: 85087888172
PURE ID: 13914334
343a03c2-6b41-4867-83b9-4dacbe23a771
ISSN: 15821838
DOI: 10.1111/jcmm.15628
metadata.dc.description.sponsorship: We thank Thomas Ricker and Alexander Trofimov for their valuable technical contribution, RSF-18-15-00357 and Neuroplast-BV (Maastricht, Netherlands) for a supply of FUS[1-359]-tg mice and ?Neuro-Cells', respectively, RFBR-18-015-00450 for a help with in vitro work and ?5-100' Russian Excellence Program for a support.
RSCF project card: 18-15-00357
Appears in Collections:Научные публикации, проиндексированные в SCOPUS и WoS CC

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