| First Author | Liu X | Year | 2022 |
| Journal | Neurobiol Dis | Volume | 175 |
| Pages | 105922 | PubMed ID | 36371059 |
| Mgi Jnum | J:334239 | Mgi Id | MGI:7407944 |
| Doi | 10.1016/j.nbd.2022.105922 | Citation | Liu X, et al. (2022) Deficiency of astrocyte CysLT(1)R ameliorates depression-like behaviors in mice by modulating glutamate synaptic transmission. Neurobiol Dis 175:105922 |
| abstractText | Our previous study suggests that hippocampal cysteinyl leukotriene receptor 1 (CysLT(1)R) could be involved in depression. Herein we hypothesize that CysLT(1)R may regulate depression by affecting synaptic glutamate cycling based on existence of CysLT(1)R in the astrocytes that participate in occurrence of depression. We found that CysLT(1)R expression was significantly increased in the astrocyte of chronic unpredictable mild stress (CUMS)-induced depression-like mice, CysLT(1)R astrocyte-specific conditional knockout (AcKO) significantly improved depression-like behaviors, as indicated by decreased immobility time in the forced swimming test and tail suspension test and increased sucrose preference in the sucrose preference test, and knockdown of CysLT(1)R in the astrocyte of dentate gyrus (DG), the region with the most significant increase of CysLT(1)R in the astrocyte of depression-like mice, produced similar effects. Correspondingly, overexpression of CysLT(1)R in the astrocyte of DG induced depression-like behaviors in mice. The further study showed that CysLT(1)R AcKO ameliorated synaptic plasticity impairment, as reflected by increased synapse, LTP and PSD95, and promoted glutamate transporter 1 (GLT-1) expression by inhibiting NF-kappaB p65 nuclear translocation mediated by beta-arestin2 and clatrhin, subsequently decreased glutamate in synaptic cleft and GluN2B on postsynaptic membrane in depression-like mice. The present study also showed that GLT-1 agonist or NF-kappaB inhibitor ameliorated depressive-like behaviors induced by overexpression of the astrocyte CysLT(1)R of DG. Our study demonstrated that astrocyte CysLT(1)R regulated depression by modulating glutamate synaptic transmission, suggesting that CysLT(1)R could be a potential target for developing novel drugs of anti-depression. |
