Drug induces depression-like phenotypes and alters gene expression profiles in Drosophila.

BACKGROUND: Major depressive disorder (MDD) is a severe mental illness that affects more than 350 million people worldwide. However, the molecular mechanisms of depression are currently unclear. Studies suggest that Drosophila and humans have similar depression-like symptoms under pressure. In this research, we choose Drosophila melanogaster as the animal model to explore the molecular mechanisms that trigger depression.

RESULTS: We found that feeding D. melanogaster with the medium containing Levodopa or Chlorpromazine could induce depression-like phenotypes in both behavioral and biochemical biomarkers, including significantly decreased food intake, mating frequency, serotonin (5-HT) concentration, and increased malondialdehyde (MDA) concentration as well as reduced activity of superoxide dismutase (SOD). Moreover, the progeny of Chlorpromazine-treated flies also showed these depression-like features. By RNA-seq technology, we identified 467 genes that were differentially expressed between Chlorpromazine treated (CPZ) and control male flies [fold-change of ≥2 (q-value<5%)]. When comparing CPZ with control flies, 312 genes were upregulated and 155 genes downregulated. Differential expression of genes related to metabolic pathway, Parkinson's disease, Huntington's disease, Alzheimer's disease and lysozyme pathways were observed. Quantitative reverse transcriptase PCR (qRT-PCR) confirmed that 19 genes are differentially expressed in CPZ and control male flies.

CONCLUSIONS: Levodopa, or Chlorpromazine can induce depression-like phenotypes in D. melanogaster regarding changes of appetite and sexual activity, and some key biochemical markers. A total of 467 genes were identified by RNA-seq analysis to have at least a 2-fold-change in expression between CPZ and control flies, including genes involved in metabolism, neurological diseases and lysozyme pathways. Our data provide additional insight into molecular mechanisms underlying depressive disorders in humans and may also contribute to clinical treatment.