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Circulating miR-9* and miR-384-5p as potential indicators for trimethyltin-induced neurotoxicity
Keiko Ogata1, Kayo Sumida2, Kaori Miyata2
1Environmental 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.
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.
Insights
Serum microRNAs (miRNAs), specifically miR-9* and miR-384-5p, show potential as novel biomarkers for detecting trimethyltin-induced neurotoxicity in rats. Their levels correlated with neural cell death, indicating promise for early diagnosis.
Area of Science:
- Biomarkers and Diagnostics
- Neurotoxicology
- Molecular Biology
Background:
- Circulating microRNAs (miRNAs) are stable, tissue-specific molecules with potential as biomarkers.
- Neurotoxicity assessment often relies on behavioral and histopathological changes, which can be late indicators.
- Identifying early, sensitive biomarkers for neurotoxicity is crucial for timely intervention.
Purpose of the Study:
- To investigate if nervous system-enriched miR-9* and hippocampus-enriched miR-384-5p in serum can indicate neurotoxicity.
- To evaluate the diagnostic potential of these miRNAs against traditional neurotoxicity assessment methods.
Main Methods:
- Rats were administered varying doses of trimethyltin (TMT) chloride.
- Serum and brain samples were collected at multiple time points post-administration.
- Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to measure miR-9* and miR-384-5p levels; neurobehavioral and histopathological analyses were also performed.
Main Results:
- TMT exposure induced observable neurotoxic symptoms and histopathological evidence of neural cell death, primarily in the hippocampus.
- Serum levels of miR-9* and miR-384-5p significantly increased in a dose- and time-dependent manner, correlating with neural damage.
- Hippocampal miRNA levels did not show significant changes, suggesting serum miRNAs are more sensitive indicators of systemic neurotoxic effects.
Conclusions:
- Elevated serum miR-9* and miR-384-5p levels serve as potential novel biomarkers for detecting trimethyltin-induced neurotoxicity.
- These circulating miRNAs may offer an earlier and more sensitive detection method compared to clinical and histopathological assessments.
- Further research is warranted to validate these findings and explore their clinical applicability in human neurotoxicity.
