Brain microRNA profiles after exposure to heroin in rats

Abstract

Heroin addiction is one of the neuropsychiatric burdens that affects many genetic and epigenetic systems. While it is known that heroin may change the expressions of some genes in the brain during dependence, there is no detailed study related to which gene are mostly affected. Therefore, in the current study, we aimed to determine alterations in the miRNA profiles of rats’ brains for providing a detailed analysis of molecular mechanisms in heroin addiction-related toxicology. Next generation global miRNA sequencing was used to predict potential miRNAs in prefrontal cortex (PC), hippocampus, ventral tegmental area (VTA), striatum, and Nucleus accumbens (NA) of rats that exposed to heroin by intravenous injections. The total daily dose was started with 2 mg/kg and ended with 10 mg/kg on the 10th day. In the striatum, miR-18a, miR-17-5p, miR-20a-5p, miR-106a, miR-301a-3p, miR872-5p, miR-15a-5p, miR-500-3p, and miR-339-5p expressions were upregulated by nearly 2-to-4 times with heroin. The expressions of hippocampal miR-153-3p, miR-130a-3p, miR-204-5p, miR-15b-5p, and miR-137-3p and the expressions of miR-872, miR-183-5p, miR-20a-5p, miR-325-5p, miR-379-5p, and miR-340-5p in the VTA were 2-times higher in the heroin-addicted rats. While there was nearly 2-times increase in the miR-129-1-3p and miR-3068-3p expressions in the NA, no change was noted in the PC due to heroin. The only heroin-dependent downregulation was observed in the expressions of striatal miR-450b-3p and miR-103-1-5p of VTA. These results suggested that heroin addiction might give harm to brain by altering cytokine balance and increasing neuroinflammation and apoptosis. In addition, neurons also try to compensate these abnormalities by enhancing neurogenesis and angiogenesis through several miRNAs in the different brain regions. In conclusion, the present study may provide a more integrated view of the molecular mechanism and a potential biomarker that will aid in clinical diagnosis and treatment of heroin-dependence.