Circulating miR-9* and miR-384-5p as Potential Indicators for Trimethyltin-induced Neurotoxicity. (February 2015)

• Record Type: Journal Article
• Authors: Ogata, Keiko; Sumida, Kayo; Miyata, Kaori; Kushida, Masahiko; Kuwamura, Mitsuru; Yamate, Jyoji
• Is Part Of: Toxicologic pathology. Volume 43:Number 2(2015)
• Page Start: 198
• Page End: 208
• Publication Date: 2015-02
• Subjects: microRNAs -- biomarker -- serum -- neurotoxicity -- trimethyltin -- hippocampus; Pathology -- Periodicals; Toxicology -- Periodicals; Pathology; Toxicology; 615.9
• DOI: 10.1177/0192623314530533
• Languages: English
• ISSNs: 0192-6233

Abstract

Circulating microRNAs (miRNAs) show promise as biomarkers due to their tissue-specific expression and high stability. This study was conducted to investigate whether nervous system–enriched miR-9* and hippocampus-enriched miR-384-5p could be indicators of neurotoxicity in serum. Rats were given a single administration of trimethyltin (TMT) chloride at 6, 9, or 12 mg/kg by gavage, and brain and serum were collected 1, 4, and 7 days after administration. MiR-9* and miR-384-5p levels in serum and hippocampus were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR), and their neurotoxicity detection sensitivities were compared with nervous symptoms, auditory response, and histopathology. TMT caused tremor, hypersensitivity, and decreased auditory response at 12 mg/kg on day 1 and at 9 mg/kg on day 4. Histopathologically, neural cell death and glial reaction were observed in brain (mainly hippocampus) at 12 mg/kg on day 1, 4, and 7 and at 6 and 9 mg/kg on day 4 and 7. MiR-9* and miR-384-5p levels were elevated in serum at 9 and 12 mg/kg on days 4 and 7 (at 9 mg/kg on day 7, miR-9* only) but were not changed in hippocampus. These miRNAs were considered to be elevated with the evolution of neural cell death and were thus considered possible novel indicators of neurotoxicity.