Tong Xiaoping's research team at Shanghai Jiaotong University reveals the "new function" of oligodendrocyte stem cells-promoting anxiety

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NG2 glial cells are also called oligodendrocyte precursor cells (OPCs).
They were first discovered in the 1980s.
They have the function of self-renewal as pluripotent stem cells and can form marrow during early brain development.
Sheath oligodendrocytes
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NG2 glial cells receive direct synaptic input from glutamatergic and GABAergic neurons, and exhibit neuronal-like long-term potentiation (LTP) at excitatory synapses, which is found in other glial cells Does not exist
.

On September 30, 2021, Tong Xiaoping's research team at Shanghai Jiaotong University School of Basic Medicine revealed that NG2 glial cells regulate the activity of internergic neurons by releasing GABA, causing excitatory/inhibitory imbalance and promoting anxiety
.

Chronic social frustration stress can simulate human stress and induce anxiety-like and depression-like behaviors in mice
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The researchers found through the optical fiber recording system that the calcium ion activity of hippocampal NG2 cells was significantly enhanced after chronic stress; light-specific activation of hippocampal NG2 cells can cause anxiety-like behavior in mice
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Why does the activation of NG2 cause anxiety-like behavior? Light-specific activation of NG2 glial cells NG2 glial cells are closely related to neurons: they can respond to vesicular or non-vesicular synaptic input, and can detect neurotransmitters in proximal neurons or unmyelinated axons.
This indicates that NG2 glial cells may affect neuronal synaptic function
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The researchers used light to specifically activate NG2 glial cells in the CA1 region of the hippocampus to promote the release of GABA, and the tonic inhibitory effect was enhanced
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Further immunofluorescence experiments found that NG2 glial cells mainly regulate the inhibitory neurons that express cholecystokinin (CCK) and neuropeptide Y (NPY) in the CA1 area
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However, NG2 glial cells in the DG region of the hippocampus regulate inhibitory neurons that express somatostatin and paralbumin
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This connection between NG2 glial cells and neurons is also reflected in the ultrastructure: further projection electron microscopy revealed that NG2 glial cells in the CA1 area of ​​the hippocampus contain a large number of vesicles, which can form pre-synaptic and post-synaptic structures with inhibitory neurons.
In other words, NG2 glial cells and inhibitory neurons do have direct synaptic input
.

In order to further understand how light-activated NG2 glial cells cause an increase in GABA release from the synaptic cleft, they used single-cell sequencing to analyze changes in signals related to GABA synthesis, transport, and metabolism, and found that it encodes glutamate decarboxylase 67 (GAD67).
) The gene Gad1 is highly expressed on NG2 glial cells
.

Subsequent immunofluorescence experiments and molecular experiments further confirmed this result
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In vitro cell experiments found that exocytosis blockers can inhibit the enhancement of tonic inhibition caused by light-activated NG2 glial cells, which indicates that NG2 glial cells can functionally promote the synaptic release of GABA through the vesicle transport mechanism
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In addition, this release process depends on the small synaptic vesicle protein VAMP-2
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In summary, this article reveals that NG2 glial cells are activated to promote the release of GABA in the synaptic cleft, which in turn regulates the inhibitory postsynaptic activity of neighboring mesenteric neurons, causing excitatory/inhibitory imbalance, and ultimately anxiety
.

[References] https://doi.
org/10.
1038/s41467-021-25956-y The pictures in the text are from the references