Astrocyte secretes IL-6 to modulate PSD-95 palmitoylation in basolateral amygdala and depression-like behaviors induced by peripheral nerve injury

Copyright © 2022 Elsevier Inc. All rights reserved..

Dysfunction of glutamatergic synaptic plasticity in basolateral amygdala (BLA) constitutes a critical pathogenic mechanism underlying the depression-like behaviors induced by chronic pain. Astrocytes serve as an important supporting cell modulating glutamatergic synaptic transmission. Here, we found that peripheral spared nerve injury (SNI) induced astrocyte activation to release IL-6 in BLA. Inhibition of astrocyte activity attenuated SNI-induced IL-6 overexpression and depression-like behaviors. Moreover, SNI enhanced the abundance of DHHC2 in synaptosome and DHHC3 in Golgi apparatus, promoted PSD-95 palmitoylation, and increased the recruitment of GluR1 and NR2B at synapses. Suppression of IL-6 or PSD-95 palmitoylation attenuated the synaptic accumulation of GluR1 and NR2B in BLA and improved depression-like behaviors induced by SNI. Furthermore, IL-6 downstream PI3K increased the expression of DHHC3 in Golgi apparatus and facilitated the interaction of palmitoylated PSD-95 with GluR1 and NR2B at synapses. These findings collectively suggested that SNI activated astrocyte to release IL-6 in BLA, which promoted PSD-95 palmitoylation and enhanced the synaptic trafficking of GluR1 and NR2B, and subsequently mediated the depression-like behaviors induced by nerve injury.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:104

Enthalten in:

Brain, behavior, and immunity - 104(2022) vom: 15. Aug., Seite 139-154

Sprache:

Englisch

Beteiligte Personen:

Liu, Lian [VerfasserIn]
Dai, Luqi [VerfasserIn]
Xu, Dan [VerfasserIn]
Wang, Yinchan [VerfasserIn]
Bai, Lin [VerfasserIn]
Chen, Xiaoting [VerfasserIn]
Li, Mengzhou [VerfasserIn]
Yang, Shuai [VerfasserIn]
Tang, Yuying [VerfasserIn]

Links:

Volltext

Themen:

Astrocyte
Basolateral amygdala
IL-6
Journal Article
PSD-95
Palmitoylation

Anmerkungen:

Date Revised 16.10.2023

published: Print-Electronic

Citation Status Publisher

doi:

10.1016/j.bbi.2022.05.014

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM34158875X