Small noncoding RNA Dysregulation is Implicated in Manganism in a Rat Model of Methylcyclopentadienyl Manganese Tricarbonyl-Induced Unrepaired Striatum Damage

Excessive accumulation of manganese in brain can cause Parkinsonian-like symptoms, known as Manganism. Methylcyclopentadienyl Manganese Tricarbonyl (MMT), a gasoline antiknock additive, is one of environmental exposures of manganese, which can lead to manganism in Rats. Though some researches showed that small non-coding RNAs (sncRNAs) were differently expressed in Parkinson’s disease (PD) patients, it was still unclear whether and how sncRNAs dysfunction appeared in Manganism. Unfartunately, transfer RNA-derived small RNAs (tsRNAs) and ribosomal RNA-derived small RNAs (rsRNAs) are highly modified, including 3’ terminal modification such as 3’-phosphate and 2’,3’-cyclic phosphate that block the adapter ligation process, and RNA methylations such as m1A, m3C, m1G and m22G that interfere with reverse transcription. Thus, sncRNAs could escape from traditional small RNA-seq. Here, we present the differential expression of sncRNAs in MMT-induced unrepaired striatum in rats compared with control group, using PANDORA-seq, which could discover the highly modified sncRNAs. By removing sncRNAs modification, we found that 599 sncRNAs were differently expressed in Striatum of MMT-treated rats compared with control group, and 1155 sncRNAs in Mn-treated vs control. Further function analysis for predicted targets of these DE-sncRNAs shown that dysregulation of sncRNAs was implicated Manganism in rats. The rats were treated as previously described(Zhu et al., 2022). Briefly, After the animals had acclimated for one week, eighteen rats containing 9 males and 9 females (220 ± 20 g, 8-weeks-old) were divided randomly into three groups: Control, MMT and positive control (MnCl2) of rats (with 3 rats in each groups/sex). The MMT group were treated with 4 mg/kg MMT (about 1 mg Mn/kg) with corn oil via the intragastrical (i.g.) route once a day, six days per week, for 8 weeks. The control group were treated with corn oil (1 ml/kg administration volume) in the meantime. The rats in the MnCl2 group were given 200 mg/kg MnCl2·4H2O (i.g.) with physiological saline (10 ml/kg administration volume). Animals were weighed daily.