Circulating miR-9* and miR-384-5p as potential indicators for trimethyltin-induced neurotoxicity.
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.
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Osaka, Japan Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan ogatak2@sc.sumitomo-chem.co.jp.
Keiko
K
Ogata
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Osaka, Japan.
Kayo
K
Sumida
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Osaka, Japan.
Kaori
K
Miyata
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Osaka, Japan.
Masahiko
M
Kushida
Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan.
Mitsuru
M
Kuwamura
Laboratory of Veterinary Pathology, Division of Veterinary Sciences, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan.
Jyoji
J
Yamate
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D006309:Hearing / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism; D035683:MicroRNAs / Q000097:blood* / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000097:blood* / Q000523:psychology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D014298:Trimethyltin Compounds / Q000633:toxicity*
C584165:MIRN384 microRNA, rat; C582333:MIRN9 microRNA, rat; D035683:MicroRNAs; D014298:Trimethyltin Compounds; C046488:trimethyltin
biomarker; hippocampus; microRNAs; neurotoxicity; serum; trimethyltin