Decoding the temporal nature of brain GR activity in the NFκB signal transition leading to depressive-like behavior.
Mol Psychiatry
; 26(9): 5087-5096, 2021 09.
Article
in English
| MEDLINE | ID: covidwho-1065838
ABSTRACT
The fine-tuning of neuroinflammation is crucial for brain homeostasis as well as its immune response. The transcription factor, nuclear factor-κ-B (NFκB) is a key inflammatory player that is antagonized via anti-inflammatory actions exerted by the glucocorticoid receptor (GR). However, technical limitations have restricted our understanding of how GR is involved in the dynamics of NFκB in vivo. In this study, we used an improved lentiviral-based reporter to elucidate the time course of NFκB and GR activities during behavioral changes from sickness to depression induced by a systemic lipopolysaccharide challenge. The trajectory of NFκB activity established a behavioral basis for the NFκB signal transition involved in three phases, sickness-early-phase, normal-middle-phase, and depressive-like-late-phase. The temporal shift in brain GR activity was differentially involved in the transition of NFκB signals during the normal and depressive-like phases. The middle-phase GR effectively inhibited NFκB in a glucocorticoid-dependent manner, but the late-phase GR had no inhibitory action. Furthermore, we revealed the cryptic role of basal GR activity in the early NFκB signal transition, as evidenced by the fact that blocking GR activity with RU486 led to early depressive-like episodes through the emergence of the brain NFκB activity. These results highlight the inhibitory action of GR on NFκB by the basal and activated hypothalamic-pituitary-adrenal (HPA)-axis during body-to-brain inflammatory spread, providing clues about molecular mechanisms underlying systemic inflammation caused by such as COVID-19 infection, leading to depression.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Receptors, Glucocorticoid
/
NF-kappa B
/
Depression
Type of study:
Prognostic study
Topics:
Long Covid
Limits:
Animals
Language:
English
Journal:
Mol Psychiatry
Journal subject:
Molecular Biology
/
Psychiatry
Year:
2021
Document Type:
Article
Affiliation country:
S41380-021-01016-1
Similar
MEDLINE
...
LILACS
LIS