A novel aptamer agent showed antidepressant function via binding 5-hydroxytryptamine receptor to block re-uptake of 5-HT

Abstract

Background & Objectives: Systematic evolution of ligands by exponential enrichment (SELEX) technology was widely used to screen the aptamers that bind the target protein safely and efficiently. Our study aimed to screen aptamers for anti-depression via binding to the 5-HTR to block 5-HT re- uptake.

Methods: The prokaryotic expression plasmid was constructed and the recombinant 5-HT1AR (mice) was expressed and purified. The ssDNA aptamer that bound 5-HT1AR specifically was screened by SELEX (Enzyme-linked Oligonucleotide assay), and the binding sites and relative binding strength of ssDNA were detected. At the same time, ssDNA aptamer inhibitory protein uptake and against depression was verified in cellular level and mouse depression model.

Results: The recombinant 5-HT1AR protein was purified successfully. After 12 rounds of positive screening and 5 rounds of negative screening, four aptamers with high affinity and specificity were obtained and the same epitope was bounded by four aptamers using ELONA (Enzyme-linked Oligonucleotide assay). The uptake of 5-HT was influenced by aptamer 18 in vitro, and the improvement of depression state in mice after intravenous injection of aptamer 18 was proved by tail suspension experiment in mice.

Conclusions: Aptamer is expected to be a new type of antidepressant, which can be used in the treatment of depression.