Increased IL-6 expression in astrocytes is associated with emotionality, alterations in central amygdala GABAergic transmission, and excitability during alcohol withdrawal.
Alcoholism
/ metabolism
Amygdala
/ metabolism
Animals
Anxiety
/ metabolism
Anxiety Disorders
/ metabolism
Astrocytes
/ metabolism
Central Amygdaloid Nucleus
/ metabolism
Depression
/ metabolism
Depressive Disorder
/ metabolism
Female
GABAergic Neurons
/ metabolism
Interleukin-6
/ biosynthesis
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Neurons
/ metabolism
Substance Withdrawal Syndrome
/ metabolism
Synaptic Transmission
/ physiology
Journal
Brain, behavior, and immunity
ISSN: 1090-2139
Titre abrégé: Brain Behav Immun
Pays: Netherlands
ID NLM: 8800478
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
15
06
2019
revised:
16
08
2019
accepted:
17
08
2019
pubmed:
23
8
2019
medline:
17
9
2020
entrez:
23
8
2019
Statut:
ppublish
Résumé
Accumulating evidence from preclinical and clinical studies has implicated a role for the cytokine IL-6 in a variety of CNS diseases including anxiety-like and depressive-like behaviors, as well as alcohol use disorder. Here we use homozygous and heterozygous transgenic mice expressing elevated levels of IL-6 in the CNS due to increased astrocyte expression and non-transgenic littermates to examine a role for astrocyte-produced IL-6 in emotionality (response to novelty, anxiety-like, and depressive-like behaviors). Our results from homozygous IL-6 mice in a variety of behavioral tests (light/dark transfer, open field, digging, tail suspension, and forced swim tests) support a role for IL-6 in stress-coping behaviors. Ex vivo electrophysiological studies of neuronal excitability and inhibitory GABAergic synaptic transmission in the central nucleus of the amygdala (CeA) of the homozygous transgenic mice revealed increased inhibitory GABAergic signaling and increased excitability of CeA neurons, suggesting a role for astrocyte produced IL-6 in the amygdala in exploratory drive and depressive-like behavior. Furthermore, studies in the hippocampus of activation/expression of proteins associated with IL-6 signal transduction and inhibitory GABAergic mechanisms support a role for astrocyte produced IL-6 in depressive-like behaviors. Our studies indicate a complex and dose-dependent relationship between IL-6 and behavior and implicate IL-6 induced neuroadaptive changes in neuronal excitability and the inhibitory GABAergic system as important contributors to altered behavior associated with IL-6 expression in the CNS.
Identifiants
pubmed: 31437534
pii: S0889-1591(19)30621-X
doi: 10.1016/j.bbi.2019.08.185
pmc: PMC6800653
mid: NIHMS1539241
pii:
doi:
Substances chimiques
IL6 protein, human
0
Interleukin-6
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
188-202Subventions
Organisme : NIAAA NIH HHS
ID : P60 AA006420
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA024484
Pays : United States
Organisme : NIAAA NIH HHS
ID : U01 AA013498
Pays : United States
Organisme : NIAAA NIH HHS
ID : U01 AA020893
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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