Deficiency of the clock gene Bmal1 affects neural progenitor cell migration

Autor: Martin Schmuck, Boris Görg, Ellen Fritsche, Charlotte von Gall, Beryl Schwarz-Herzke, Marion Victor, Katharina Dach, Amira A. H. Ali, Benita Sahlender, Andreas Kremer, Shakila Mir
Přispěvatelé: Pathology
Rok vydání: 2019
Předmět:
Male
Time Factors
RNA oxidation
Rostral migratory stream
0302 clinical medicine
Neural Stem Cells
Cell Movement
Phosphorylation
Cells
Cultured
Cytoskeleton
chemistry.chemical_classification
Mice
Knockout
Filopodia
biology
Chemistry
General Neuroscience
05 social sciences
Neurogenesis
Circadian
ARNTL Transcription Factors
Gene Expression Regulation
Developmental
Catalase
Olfactory Bulb
Neural stem cell
Cell biology
medicine.anatomical_structure
Phenotype
Original Article
Anatomy
Signal Transduction
Cofilin 1
endocrine system
Histology
Genotype
Subventricular zone
050105 experimental psychology
03 medical and health sciences
otorhinolaryngologic diseases
medicine
Animals
0501 psychology and cognitive sciences
Progenitor cell
Clock genes
Reactive oxygen species
Hydrogen peroxide
Olfactory bulb
p-Cofilin
Mice
Inbred C57BL
stomatognathic diseases
Oxidative Stress
Bmal1
biology.protein
Reactive Oxygen Species
030217 neurology & neurosurgery
Zdroj: Brain Structure & Function
Brain Structure & Function, 224(1), 373-386. Springer-Verlag
ISSN: 1863-2653
DOI: 10.1007/s00429-018-1775-1
Popis: We demonstrate the impact of a disrupted molecular clock in Bmal1-deficient (Bmal1−/−) mice on migration of neural progenitor cells (NPCs). Proliferation of NPCs in rostral migratory stream (RMS) was reduced in Bmal1−/− mice, consistent with our earlier studies on adult neurogenesis in hippocampus. However, a significantly higher number of NPCs from Bmal1−/− mice reached the olfactory bulb as compared to wild-type littermates (Bmal1+/+ mice), indicating a higher migration velocity in Bmal1−/− mice. In isolated NPCs from Bmal1−/− mice, not only migration velocity and expression pattern of genes involved in detoxification of reactive oxygen species were affected, but also RNA oxidation of catalase was increased and catalase protein levels were decreased. Bmal1+/+ migration phenotype could be restored by treatment with catalase, while treatment of NPCs from Bmal1+/+ mice with hydrogen peroxide mimicked Bmal1−/− migration phenotype. Thus, we conclude that Bmal1 deficiency affects NPC migration as a consequence of dysregulated detoxification of reactive oxygen species. Electronic supplementary material The online version of this article (10.1007/s00429-018-1775-1) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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