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

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Leanne M Holt ◽  
Raymundo D Hernandez ◽  
Natasha L Pacheco ◽  
Beatriz Torres Ceja ◽  
Muhannah Hossain ◽  
...  
Keyword(s):  
Growth Factor ◽  
Neurotrophic Factor ◽  
Neuronal Morphology ◽  
Cns Development ◽  
Protein Coding ◽  
Morphological Complexity ◽  
Mature Astrocyte ◽  
Bdnf Signaling ◽  
Morphological Maturation ◽  
Critical Process

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.

scholarly journals BDNF/TrkB.T1 signaling is a novel mechanism for astrocyte morphological maturation

2019 ◽  
Author(s):  
Leanne M. Holt ◽  
Natasha L. Pacheco ◽  
Raymundo Hernandez ◽  
Muhannah Hossain ◽  
Michelle L. Olsen
Keyword(s):  
Growth Factor ◽  
Neurotrophic Factor ◽  
Neuronal Morphology ◽  
Cns Development ◽  
Protein Coding ◽  
Morphological Complexity ◽  
Mature Astrocyte ◽  
Morphological Maturation ◽  
Critical Process

AbstractBrain 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.

scholarly journals Modulation of Brain-Derived Neurotrophic Factor (BDNF) Signaling Pathway by Culinary Sage (Salvia officinalis L.)

2021 ◽  
Vol 22 (14) ◽  
pp. 7382
Author(s):  
Nancy Chiang ◽  
Shahla Ray ◽  
Jade Lomax ◽  
Sydney Goertzen ◽  
Slavko Komarnytsky ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Neurotrophic Factor ◽  
High Performance ◽  
Memory Function ◽  
Brain Derived Neurotrophic Factor ◽  
Salvia Officinalis ◽  
C6 Glioma Cells ◽  
Medicinal Uses ◽  
Bdnf Signaling ◽  
Salvia Officinalis L

Culinary sage (Salvia officinalis L.) is a common spice plant in the mint family (Lamiaceae) well known for its distinctive culinary and traditional medicinal uses. Sage tea has been used traditionally as a brain-enhancing tonic and extracts from sage have been reported to have both cognitive and memory enhancing effects. Brain-derived neurotrophic factor (BDNF) is an endogenous signaling molecule involved in cognition and memory function. In this study, activity-guided fractionation employing preparative reverse-phase high performance liquid chromatography (RP-HPLC) of culinary sage extracts led to the discovery of benzyl 6-O-β-D-apiofuranosyl-β-D-glucoside (B6AG) as a natural product that upregulates transcription of neurotrophic factors in C6 glioma cells. Purified B6AG showed a moderate dose response, with upregulation of BDNF and with EC50 at 6.46 μM. To better understand the natural variation in culinary sage, B6AG was quantitated in the leaves of several commercial varieties by liquid chromatography-mass spectrometry (LC-MS). The level of B6AG in dried culinary sage was found to range from 334 ± 14 to 698 ± 65 μg/g. This study provided a foundation for future investigations, including quantitative inquiries on the distribution of B6AG within the different plant organs, explorations in optimizing post-harvest practices, and aid in the development of sage varieties with elevated levels of B6AG.

scholarly journals Watching Neurons Hand Off Molecules

2002 ◽  
Vol 10 (1) ◽  
pp. 3-34
Author(s):  
Stephen W. Carmichael
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Neurotrophic Factors ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Target Cells ◽  
Nerve Growth ◽  
Hand Off ◽  
Presynaptic Neurons

Since the discovery of nerve growth factor, it has been thought that neurotrophic factors are released or secreted from target cells. However, more recently it has been suggested that a specific neurotrophic factor known as brain-derived neurotrophic factor (BDNF) may reach target cells directly from pre-synaptic axons. It has not been known how these molecules get from the neuron in which they are produced to the target cells. Keigo Kohara, Akihiko Kitamura, Mieko Morishima, and Tadaharu Tsumoto have demonstrated that BDNF is transported anterogradely from presynaptic neurons to target neurons.

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