Back to Search
Start Over
Menin Deficiency Leads to Depressive-like Behaviors in Mice by Modulating Astrocyte-Mediated Neuroinflammation.
- Source :
-
Neuron [Neuron] 2018 Nov 07; Vol. 100 (3), pp. 551-563.e7. Date of Electronic Publication: 2018 Sep 13. - Publication Year :
- 2018
-
Abstract
- Astrocyte dysfunction and inflammation are associated with the pathogenesis of major depressive disorder (MDD). However, the mechanisms underlying these effects remain largely unknown. Here, we found that multiple endocrine neoplasia type 1 (Men1; protein: menin) expression is attenuated in the brain of mice exposed to CUMS (chronic unpredictable mild stress) or lipopolysaccharide. Astrocyte-specific reduction of Men1 (GcKO) led to depressive-like behaviors in mice. We observed enhanced NF-κB activation and IL-1β production with menin deficiency in astrocytes, where depressive-like behaviors in GcKO mice were restored by NF-κB inhibitor or IL-1β receptor antagonist. Importantly, we identified a SNP, rs375804228, in human MEN1, where G503D substitution is associated with a higher risk of MDD onset. G503D substitution abolished menin-p65 interactions, thereby enhancing NF-κB activation and IL-1β production. Our results reveal a distinct astroglial role for menin in regulating neuroinflammation in depression, indicating that menin may be an attractive therapeutic target in MDD.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Animals
Astrocytes pathology
Cells, Cultured
Depressive Disorder, Major genetics
Depressive Disorder, Major psychology
Female
Humans
Inflammation genetics
Inflammation metabolism
Inflammation psychology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Middle Aged
Proto-Oncogene Proteins genetics
Stress, Psychological genetics
Stress, Psychological psychology
Astrocytes metabolism
Depressive Disorder, Major metabolism
Proto-Oncogene Proteins deficiency
Stress, Psychological metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4199
- Volume :
- 100
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Neuron
- Publication Type :
- Academic Journal
- Accession number :
- 30220511
- Full Text :
- https://doi.org/10.1016/j.neuron.2018.08.031