Astrocyte morphogenesis is dependent on BDNF signaling via astrocytic TrkB.T1

Autor: Beatriz Torres Ceja, Michelle L. Olsen, Raymundo D Hernandez, Muhannah Hossain, Natasha L. Pacheco, Leanne M. Holt
Rok vydání: 2019
Předmět:
Mouse
medicine.medical_treatment
Synaptogenesis
Tropomyosin receptor kinase B
Synapse
Mice
0302 clinical medicine
Neurotrophic factors
Protein Isoforms
Biology (General)
Receptor
Cells
Cultured
Mice
Knockout
0303 health sciences
synaptogenesis
Membrane Glycoproteins
musculoskeletal
neural
and ocular physiology
General Neuroscience
TrkB
Cell Differentiation
General Medicine
Protein-Tyrosine Kinases
Cell biology
medicine.anatomical_structure
embryonic structures
Medicine
Research Article
Signal Transduction
Astrocyte
QH301-705.5
Science
Morphogenesis
morphogenesis
Biology
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
astrocyte
medicine
Animals
development
030304 developmental biology
General Immunology and Microbiology
Brain-Derived Neurotrophic Factor
Growth factor
BDNF
nervous system
Astrocytes
030217 neurology & neurosurgery
Neuroscience
Zdroj: eLife
eLife, Vol 8 (2019)
ISSN: 2050-084X
DOI: 10.7554/elife.44667
Popis: Brain-derived neurotrophic factor (BDNF) is a critical growth factor involved in the maturation of the CNS, including neuronal morphology and synapse refinement. Herein, we demonstrate astrocytes express high levels of BDNF’s receptor, TrkB (in the top 20 of protein-coding transcripts), with nearly exclusive expression of the truncated isoform, TrkB.T1, which peaks in expression during astrocyte morphological maturation. Using a novel culture paradigm, we show that astrocyte morphological complexity is increased in the presence of BDNF and is dependent upon BDNF/TrkB.T1 signaling. Deletion of TrkB.T1, globally and astrocyte-specifically, in mice revealed morphologically immature astrocytes with significantly reduced volume, as well as dysregulated expression of perisynaptic genes associated with mature astrocyte function. Indicating a role for functional astrocyte maturation via BDNF/TrkB.T1 signaling, TrkB.T1 KO astrocytes do not support normal excitatory synaptogenesis or function. These data suggest a significant role for BDNF/TrkB.T1 signaling in astrocyte morphological maturation, a critical process for CNS development.
Databáze: OpenAIRE
Externí odkaz: