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

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dc.contributor.authorHolt, Leanne M.en
dc.contributor.authorHernandez, Raymundo D.en
dc.contributor.authorPacheco, Natasha L.en
dc.contributor.authorCeja, Beatriz Torresen
dc.contributor.authorHossain, Muhannahen
dc.contributor.authorOlsen, Michelle L.en
dc.contributor.departmentSchool of Neuroscienceen
dc.date.accessioned2019-10-18T14:41:46Zen
dc.date.available2019-10-18T14:41:46Zen
dc.date.issued2019-08-21en
dc.description.abstractBrain-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.en
dc.description.notesNational Institute of Neurological Disorders and Stroke F31NS100259 Leanne M Holt; National Institute of Neurological Disorders and Stroke R01NS075062 Michelle Olsen; The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.en
dc.description.sponsorshipNational Institute of Neurological Disorders and StrokeUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Neurological Disorders & Stroke (NINDS) [F31NS100259, R01NS075062]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.7554/eLife.44667en
dc.identifier.issn2050-084Xen
dc.identifier.othere44667en
dc.identifier.pmid31433295en
dc.identifier.urihttp://hdl.handle.net/10919/94635en
dc.identifier.volume8en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectneurotrophic factoren
dc.subjectglutamate transportersen
dc.subjectstructural plasticityen
dc.subjectsecreted proteinsen
dc.subjectmessenger-rnaen
dc.subjectrat-brainen
dc.subjectexpressionen
dc.subjectreceptoren
dc.subjectmorphologyen
dc.subjectgliaen
dc.titleAstrocyte morphogenesis is dependent on BDNF signaling via astrocytic TrkB.T1en
dc.title.serialeLifeen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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Destination Area: Adaptive Brain and Behavior (ABB)