Loss of liver X receptor β in astrocytes leads to anxiety-like behaviors via regulating synaptic transmission in the medial prefrontal cortex in mice

Xin Li, Hongyu Zhong, Zhongke Wang, Rui Xiao, Per Antonson, Tianyao Liu, Chuan Wu, Jiao Zou, Lian Wang, Ivan Nalvarte, Haiwei Xu, Margaret Warner, Jan Ake Gustafsson, Xiaotang Fan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Astrocytes are integral components of synaptic transmission, and their dysfunction leads to neuropsychiatric disorders such as anxiety and depression. Liver X receptor β (LXRβ) is expressed in astrocytes, and LXRβ global knockout mice shows impaired synaptic formation. In order to define the role of LXRβ in astrocytes, we used a conditional Cre-loxP system to specifically remove LXRβ from astrocytes. We found that this deletion caused anxiety-like but not depressive-like behaviors in adult male mice. This behavioral phenotype could be completely reproduced by selective deletion of LXRβ in astrocytes in the medial prefrontal cortex (mPFC). Pyramidal neurons in layer V of mPFC are involved in mood behaviors. We found that there was an increased spontaneous excitatory synaptic transmission in layer V pyramidal neurons of the mPFC of these mice. This was concurrent with increased dendritic complexity, despite normal appearance and number of dendritic spines. In addition, gene ontology analysis of RNA sequencing revealed that deletion of astrocytic LXRβ led to the enrichment of the process of synaptic transmission in mPFC. Finally, we also confirmed that renormalized excitatory synaptic transmission in layer V pyramidal neurons alleviated the anxiety in mice with astrocytic LXRβ deletion in mPFC. Together, our findings reveal that astrocytic LXRβ in mPFC is critical in the regulation of synaptic transmission, and this provides a potential new target for treatment of anxiety-like behavior.

Original languageEnglish (US)
Pages (from-to)6380-6393
Number of pages14
JournalMolecular Psychiatry
Volume26
Issue number11
DOIs
StatePublished - Nov 2021

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

Fingerprint

Dive into the research topics of 'Loss of liver X receptor β in astrocytes leads to anxiety-like behaviors via regulating synaptic transmission in the medial prefrontal cortex in mice'. Together they form a unique fingerprint.

Cite this