BDNF/TrkB.T1 signaling is a novel mechanism for astrocyte morphological maturation
| Autor: | Muhannah Hossain, Leanne M. Holt, Michelle L. Olsen, Raymundo D Hernandez, Natasha L. Pacheco |
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| Rok vydání: | 2019 |
| Předmět: |
Gene isoform
Brain-derived neurotrophic factor 0303 health sciences musculoskeletal neural and ocular physiology Growth factor medicine.medical_treatment Synaptogenesis Tropomyosin receptor kinase B Biology Cell biology Synapse 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure nervous system medicine Receptor 030217 neurology & neurosurgery 030304 developmental biology Astrocyte |
| DOI: | 10.1101/518787 |
| Popis: | Brain derived neurotrophic factor (BDNF) is a critical growth factor involved in the maturation of neurons, 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 in vivo revealed morphologically immature astrocytes with significantly reduced volume and branching, as well as dysregulated expression of perisynaptic genes associated with mature astrocyte functions, including synaptogenic genes. Indicating a role for functional astrocyte maturation via BDNF/TrkB.T1 signaling, TrkB.T1 KO astrocytes do not support normal excitatory synaptogenesis. These data suggest a significant role for BDNF/TrkB.T1 signaling in astrocyte morphological maturation, a critical process for CNS development. |
| Databáze: | OpenAIRE |
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