Asset Details
Do you wish to reserve the book?
Glioma synapses recruit mechanisms of adaptive plasticity
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Glioma synapses recruit mechanisms of adaptive plasticity
Do you wish to request the book?
Glioma synapses recruit mechanisms of adaptive plasticity
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Glioma synapses recruit mechanisms of adaptive plasticity
2023
Overview
The role of the nervous system in the regulation of cancer is increasingly appreciated. In gliomas, neuronal activity drives tumour progression through paracrine signalling factors such as neuroligin-3 and brain-derived neurotrophic factor
1
–
3
(BDNF), and also through electrophysiologically functional neuron-to-glioma synapses mediated by AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors
4
,
5
. The consequent glioma cell membrane depolarization drives tumour proliferation
4
,
6
. In the healthy brain, activity-regulated secretion of BDNF promotes adaptive plasticity of synaptic connectivity
7
,
8
and strength
9
–
15
. Here we show that malignant synapses exhibit similar plasticity regulated by BDNF. Signalling through the receptor tropomyosin-related kinase B
16
(TrkB) to CAMKII, BDNF promotes AMPA receptor trafficking to the glioma cell membrane, resulting in increased amplitude of glutamate-evoked currents in the malignant cells. Linking plasticity of glioma synaptic strength to tumour growth, graded optogenetic control of glioma membrane potential demonstrates that greater depolarizing current amplitude promotes increased glioma proliferation. This potentiation of malignant synaptic strength shares mechanistic features with synaptic plasticity
17
–
22
that contributes to memory and learning in the healthy brain
23
–
26
. BDNF–TrkB signalling also regulates the number of neuron-to-glioma synapses. Abrogation of activity-regulated BDNF secretion from the brain microenvironment or loss of glioma TrkB expression robustly inhibits tumour progression. Blocking TrkB genetically or pharmacologically abrogates these effects of BDNF on glioma synapses and substantially prolongs survival in xenograft models of paediatric glioblastoma and diffuse intrinsic pontine glioma. Together, these findings indicate that BDNF–TrkB signalling promotes malignant synaptic plasticity and augments tumour progression.
In glioma, malignant synapses hijack mechanisms of synaptic plasticity to increase glutamate-dependent currents in tumour cells and the formation of neuron–glioma synapses, thereby promoting tumour proliferation and progression.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/106
/ 13/51
/ 14
/ 14/19
/ 14/28
/ 38
/ 38/91
/ 82
/ 82/51
/ Animals
/ Brain
/ Brain-derived neurotrophic factor
/ Brain-Derived Neurotrophic Factor - metabolism
/ Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism
/ Child
/ CRISPR
/ Glioma
/ Humanities and Social Sciences
/ Humans
/ Kinases
/ Ligands
/ Neurons
/ Receptors, AMPA - metabolism
/ Science
/ Synapses
/ Tumors
/ α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
/ α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors
