Highlights
- •Astrocytes in rACC contribute to the maintenance of stress-related VH.
- •Upregulated TSP1 and BDNF induced by astrocytic activation may mediate the effect of astrocytes on VH.
- •STAT1 is a downstream mediator of ERK signaling, resulting in VH via activating astrocytes.
Abstract
The rostral anterior cingulate cortex (rACC) has been found to be an important brain
region in mediating visceral hypersensitivity. However, the underlying mechanisms
remain unclear. This study aimed to explore the role of astrocytes in the maintenance
of visceral hypersensitivity induced by chronic water avoidance stress (WAS) as well
as the potential signaling pathway that activates astrocytes in the rACC. We found
that ACC-reactive astrogliosis resulted in the overexpression of c-fos, TSP-1, and
BDNF in stress-related visceral hypersensitivity rats. Visceral hypersensitivity was
reversed by pharmacological inhibition of astrocytic activation after WAS, as were
the overexpression of c-fos, TSP-1 and BDNF. Activation of the astrocytic Gi-pathway
increased the visceral sensitivity and expression of c-fos, TSP-1, and BDNF. Visceral
hypersensitivity was also ameliorated by the pharmacological inhibition of ERK and
STAT1 phosphorylation after WAS. Furthermore, inhibition of the ERK-STAT1 cascade
reduced astrocytic activation. These findings suggest that astrocytic ERK/STAT1 signaling
in the rACC contributes to the maintenance of stress-related visceral hypersensitivity.
Perspective
Visceral hypersensitivity is a key factor in the pathophysiology of irritable bowel
syndrome. This study highlights the important role of astrocytic ERK/STAT1 signaling
in activating astrocytes in the rostral anterior cingulate cortex, which contributes
to visceral hypersensitivity.
Key Words
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Article info
Publication history
Published online: July 28, 2022
Accepted:
July 20,
2022
Received in revised form:
July 19,
2022
Received:
November 25,
2021
Footnotes
Conflict of interest statement: This work was supported by National Natural Science Foundation of China (grant No. 81974067), Shanghai Informatization Development Special project (202001003), Psychosomatic Medicine Project of Key Developing Disciplines of Shanghai Municipal Health Commission (2019ZB0202). We declared that there was no conflict of interest in this study.
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© 2022 by United States Association for the Study of Pain, Inc.
