Circulating miR-9 and miR-384-5p as potential indicators for trimethyltin-induced neurotoxicity

• Published in: Toxicologic pathology Vol. 43; no. 2; p. 198
• Main Authors: Ogata, Keiko, Sumida, Kayo, Miyata, Kaori, Kushida, Masahiko, Kuwamura, Mitsuru, Yamate, Jyoji
• Format: Journal Article
• Language: English
• Published: United States 01.02.2015
• Subjects: Animals; Apoptosis - drug effects; Body Weight - drug effects; Brain - drug effects; Brain - pathology; Hearing - drug effects; Hippocampus - metabolism; MicroRNAs - blood; MicroRNAs - metabolism; Motor Activity - drug effects; Neuroglia - pathology; Neurons - pathology; Neurotoxicity Syndromes - blood; Neurotoxicity Syndromes - psychology; Organ Size - drug effects; Rats; Trimethyltin Compounds - toxicity; microRNAs; trimethyltin; neurotoxicity; hippocampus; biomarker; serum
• ISSN: 1533-1601
• DOI: 10.1177/0192623314530533

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.