Molecular and behavioural abnormalities in the FUS-tg mice mimic frontotemporal lobar degeneration
| Autor: | Diana Babaevskaya, Andrey Proshin, Igor Pomytkin, Margarita Oplatchikova, Tatyana Strekalova, Johannes P.J.M. de Munter, D. A. Pavlov, Allan V. Kalueff, Klaus-Peter Lesch, Ekaterina Lysikova, Anna Gorlova, Erik Ch. Wolters, Aleksei Umriukhin |
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| Přispěvatelé: | Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Pathology amyotrophic lateral sclerosis PROTEIN EXPRESSION EXPERIMENTAL NEUROINFLAMMATION REAL TIME POLYMERASE CHAIN REACTION MOUSE ANIMAL EXPERIMENT stem cell therapy FUS[1‐359]‐tg mice Mice 0302 clinical medicine SUCROSE PREFERENCE TEST CELECOXIB BRAIN MUTATION FUS[1-359]-tg mice Neurons RNA BINDING PROTEIN FUS Behavior Animal celecoxib LOCOMOTION Neurodegeneration TRANSGENIC MOUSE Brain DEPRESSION Riluzole Spinal Cord 030220 oncology & carcinogenesis RNA ISOLATION CALCIUM BINDING PROTEIN DRUG EFFECT medicine.medical_specialty Short Communication Short Communications FUS PROTEIN MOUSE IONIZED CALCIUM BINDING ADAPTOR MOLECULE 1 BEHAVIOR ANIMAL INTERLEUKIN-1BETA NEUROINFLAMMATION 03 medical and health sciences TAIL SUSPENSION TEST NONHUMAN Social Behavior ELEVATED PLUS MAZE TEST INTERLEUKIN 1BETA FRONTOTEMPORAL LOBAR DEGENERATION Glycogen Synthase Kinase 3 beta animal model ANIMALS ANIMAL medicine.disease FUS[1-359]-TG MICE Molecular medicine 030104 developmental biology Mutation HIPPOCAMPUS emotionality and cognition CYCLOOXYGENASE 1 HOME-CAGE ACTIVITY TEST ABNORMAL BEHAVIOR SPINAL CORD GELATINASE B CYCLOOXYGENASE 2 0301 basic medicine MATRIX METALLOPROTEINASES NERVE CELL Interleukin-1beta Anti-Inflammatory Agents Hippocampus PREFRONTAL CORTEX ANIMAL MODEL UNCLASSIFIED DRUG neuroinflammation MARBLE BURYING TEST ANXIETY COGNITIVE DEFECT TISSUE INHIBITOR OF METALLOPROTEINASE 1 PLASTICITY Amyotrophic lateral sclerosis NEURONS MOLECULAR MARKER Frontotemporal lobar degeneration STEM CELL riluzole Muscle atrophy GENOTYPE ANTIINFLAMMATORY ACTIVITY frontotemporal lobar degeneration BIOLOGICAL MARKER GLYCOGEN SYNTHASE KINASE 3BETA Molecular Medicine AMYOTROPHIC LATERAL SCLEROSIS RNA-BINDING PROTEIN FUS medicine.symptom ANTIINFLAMMATORY AGENT medicine.drug STEM CELL THERAPY GLYCOGEN SYNTHASE KINASE 3 BETA CAGE TEST METABOLISM ADULT INFLAMMATION WESTERN BLOTTING ANIMAL TISSUE GENE MUTATION OPEN FIELD TEST EMOTION medicine Animals RESIDENT-INTRUDER TEST ARTICLE NERVE DEGENERATION Neuroinflammation Inflammation MALE TUMOR NECROSIS FACTOR INTRACEREBROVENTRICULAR DRUG ADMINISTRATION business.industry SOCIAL BEHAVIOR ANTI-INFLAMMATORY AGENTS Cell Biology FRONTOTEMPORAL DEMENTIA ANIMAL BEHAVIOR EMOTIONALITY AND COGNITION CONTROLLED STUDY MICE GLYCOGEN SYNTHASE KINASE 3ALPHA Cyclooxygenase 2 RILUZOLE COGNITION RNA-Binding Protein FUS business |
| Zdroj: | Journal of Cellular and Molecular Medicine, 24(17), 10251-10257. Wiley-Blackwell Journal of Cellular and Molecular Medicine J. Cell. Mol. Med. |
| ISSN: | 1582-4934 1582-1838 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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