Glioma induces atypical depression-like behaviors in mice through the 5-HT and glutamatergic synapse pathways.

Glioma patients often undertake psychiatric disorders such as depression and anxiety. There are several clinical epidemiological studies on glioma-associated depression, but basic research and corresponding animal experiments are still lacking. Here, we observed that glioma-bearing mice exhibited atypical depression-like behaviors in orthotopic glioma mouse models. The concentrations of monoamine neurotransmitters were detected by enzyme-linked immunosorbent assay (ELISA), revealing a decrease in 5-hydroxytryptamine (5-HT) levels in para-glioma tissues. The related gene expression levels also altered, detected by quantitative RT-PCR. Then, we developed a glioma-depression comorbidity mouse model. Through sucrose preference test (SPT), forced swimming test (FST), tail suspension test (TST) and other tests, we found that the occurrence of glioma could lead to changes in depression-like behaviors in a chronic unpredictable mild stress (CUMS) mouse model. The results of RNA sequencing (RNA-seq) indicated that the altered expression of glutamatergic synapse related genes in the paratumor tissues might be one of the main molecular features of the comorbidity model. Our findings suggested that the presence of glioma caused and altered depression-like behaviors, which was potentially related to the 5-HT and glutamatergic synapse pathways.