| First Author | Leng L | Year | 2018 |
| Journal | Neuron | Volume | 100 |
| Issue | 3 | Pages | 551-563.e7 |
| PubMed ID | 30220511 | Mgi Jnum | J:269857 |
| Mgi Id | MGI:6269313 | Doi | 10.1016/j.neuron.2018.08.031 |
| Citation | Leng L, et al. (2018) Menin Deficiency Leads to Depressive-like Behaviors in Mice by Modulating Astrocyte-Mediated Neuroinflammation. Neuron 100(3):551-563.e7 |
| abstractText | 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-kappaB activation and IL-1beta production with menin deficiency in astrocytes, where depressive-like behaviors in GcKO mice were restored by NF-kappaB inhibitor or IL-1beta 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-kappaB activation and IL-1beta 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. |
