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Click on the blue to follow our dystrophin gene DAG1 contains two exons encoding a single polypeptide, which are post-translationally modified to produce α-dystrophin (α-DG) and β-dystrophin (β-DG)
.
Among them, α-DG is the main component of dystrophin-glycoprotein complex (DGC), which is a high-affinity receptor for the extracellular matrix
.
The function of α-DG mainly depends on the glycosylation process to form GLY-α-DG that can bind to the ligand
.
More and more evidence shows that depression is related to GABAergic synaptic transmission dysfunction: the concentration of GABA in cerebrospinal fluid and cortical tissue is reduced, and the expression of type A gamma-aminobutyric acid receptor (GABAAR) is reduced
.
In the central nervous system, DGC mainly combines with GABAAR
.
GLY-α-DG is expressed in the post-synaptic dense part of the inhibitory synapse of pyramidal neurons and is co-localized with GABAAR
.
On November 9, 2021, Professor Chen Jianguo and Wang Fang's research team from Tongji Medical College of Huazhong University of Science and Technology revealed that GLY-α-DG protein participates in the process of depression by regulating the GABA function of the ventral hippocampus
.
Prefrontal cortex, caudate putamen, nucleus accumbens, stiff nucleus, lateral amygdala, hippocampus and other brain areas are closely related to depression
.
The researchers found that only the expression of α-DG and GLY-α-DG protein in the hippocampus decreased, and the expression of the GABAA receptor γ2 subunit on the cell membrane also decreased, especially in the ventral hippocampus
.
After shRNA virus silencing strategy specifically reduces the level of GLY-α-DG protein in the ventral hippocampus, it can promote the sensitivity of mice to stress
.
This indicates that GLY-α-DG protein plays an important role in the occurrence of depression
.
The extracellular matrix protein Agrin is an extracellular ligand of GLY-α-DG, which regulates nerve regeneration and synaptic homeostasis plasticity
.
They screened out Agrin's antidepressant effect through tail suspension experiments.
In order to further confirm this effect, specific injection of Agrin into the hippocampus for 3 consecutive days can significantly improve stress-induced depression-like behavior, and this improvement effect can last for a week
.
Electrophysiological experiments found that the magnitude of the small inhibitory postsynaptic currents (mIPSCs) in the ventral hippocampus of depression-like mice was reduced, which indicated that chronic stress impaired GABAergic synaptic transmission
.
Agrin can promote the expression of GABAA receptor γ2 subunit on the ventral hippocampal cell membrane, and reverse the GABAergic synaptic transmission disorder
.
Acetyl glucosamine transferase-like protein (LARGE) is a glycosyltransferase that is closely related to the glycosylation of α-DG
.
The level of LARGE protein in the ventral hippocampus decreased after chronic stress
.
The level of GLY-α-DG is also increased after LARGE is overexpressed by the virus, and at the same time it reduces the immobility time in the tail suspension experiment and forced swimming, and exerts an antidepressant effect
.
Previous studies have shown that α-DG is expressed on neurons and astrocytes
.
However, the changes in GLY-α-DG levels caused by chronic stress almost only occurred on neurons, and did not change on astrocytes
.
Furthermore, the virus-specific overexpression of LARG on neurons through neuron promoters also exerts a significant antidepressant effect
.
This indicates that GLY-α-DG, which is specifically expressed by neurons, regulates the occurrence of depression
.
In summary, this article reveals that GLY-α-DG in the ventral hippocampus mediates the pathogenesis of depression by regulating the expression of GABAA receptors on the membrane and GABAergic synaptic transmission
.
[References] https://doi.
org/10.
1016/j.
biopsych.
2021.
10.
022 The pictures in the article are from the references
.
Among them, α-DG is the main component of dystrophin-glycoprotein complex (DGC), which is a high-affinity receptor for the extracellular matrix
.
The function of α-DG mainly depends on the glycosylation process to form GLY-α-DG that can bind to the ligand
.
More and more evidence shows that depression is related to GABAergic synaptic transmission dysfunction: the concentration of GABA in cerebrospinal fluid and cortical tissue is reduced, and the expression of type A gamma-aminobutyric acid receptor (GABAAR) is reduced
.
In the central nervous system, DGC mainly combines with GABAAR
.
GLY-α-DG is expressed in the post-synaptic dense part of the inhibitory synapse of pyramidal neurons and is co-localized with GABAAR
.
On November 9, 2021, Professor Chen Jianguo and Wang Fang's research team from Tongji Medical College of Huazhong University of Science and Technology revealed that GLY-α-DG protein participates in the process of depression by regulating the GABA function of the ventral hippocampus
.
Prefrontal cortex, caudate putamen, nucleus accumbens, stiff nucleus, lateral amygdala, hippocampus and other brain areas are closely related to depression
.
The researchers found that only the expression of α-DG and GLY-α-DG protein in the hippocampus decreased, and the expression of the GABAA receptor γ2 subunit on the cell membrane also decreased, especially in the ventral hippocampus
.
After shRNA virus silencing strategy specifically reduces the level of GLY-α-DG protein in the ventral hippocampus, it can promote the sensitivity of mice to stress
.
This indicates that GLY-α-DG protein plays an important role in the occurrence of depression
.
The extracellular matrix protein Agrin is an extracellular ligand of GLY-α-DG, which regulates nerve regeneration and synaptic homeostasis plasticity
.
They screened out Agrin's antidepressant effect through tail suspension experiments.
In order to further confirm this effect, specific injection of Agrin into the hippocampus for 3 consecutive days can significantly improve stress-induced depression-like behavior, and this improvement effect can last for a week
.
Electrophysiological experiments found that the magnitude of the small inhibitory postsynaptic currents (mIPSCs) in the ventral hippocampus of depression-like mice was reduced, which indicated that chronic stress impaired GABAergic synaptic transmission
.
Agrin can promote the expression of GABAA receptor γ2 subunit on the ventral hippocampal cell membrane, and reverse the GABAergic synaptic transmission disorder
.
Acetyl glucosamine transferase-like protein (LARGE) is a glycosyltransferase that is closely related to the glycosylation of α-DG
.
The level of LARGE protein in the ventral hippocampus decreased after chronic stress
.
The level of GLY-α-DG is also increased after LARGE is overexpressed by the virus, and at the same time it reduces the immobility time in the tail suspension experiment and forced swimming, and exerts an antidepressant effect
.
Previous studies have shown that α-DG is expressed on neurons and astrocytes
.
However, the changes in GLY-α-DG levels caused by chronic stress almost only occurred on neurons, and did not change on astrocytes
.
Furthermore, the virus-specific overexpression of LARG on neurons through neuron promoters also exerts a significant antidepressant effect
.
This indicates that GLY-α-DG, which is specifically expressed by neurons, regulates the occurrence of depression
.
In summary, this article reveals that GLY-α-DG in the ventral hippocampus mediates the pathogenesis of depression by regulating the expression of GABAA receptors on the membrane and GABAergic synaptic transmission
.
[References] https://doi.
org/10.
1016/j.
biopsych.
2021.
10.
022 The pictures in the article are from the references
