Anri Hirai

Neonicotinoid (NN) pesticides are widely used globally, but recent studies suggest that even nontoxic doses can induce anxiety-like behaviors and alter brain monoamine neurotransmitter levels in mice. Current neurotoxicity assays may fail to detect subtle toxic effects, such as higher brain function abnormalities caused by small molecule disruptions. These findings highlight the need for highly sensitive and reproducible neurotoxicity testing methods. The brain, a lipid-rich organ, relies on lipids for various functions, and disturbances in lipid homeostasis are linked to numerous diseases. This study uses lipidomics to analyze the cerebral cortex of mice exposed to the NN acetamiprid (ACE), aiming to identify lipid biomarkers of neurotoxicity. Thirty 12-week-old male C57BL/6J mice were randomly divided into control (0 mg/kg), low dose (65 mg/kg), and high dose (130 mg/kg) groups, with 10 mice in each group. Mice were euthanized, and cerebral cortex samples were collected 30 min after oral ACE administration. Lipids were extracted and analyzed using liquid chromatography–quadrupole time-of-flight mass spectrometry. A total of 358 lipids were annotated. Fifteen lipids exhibited a fold-change > 2.0 and significant differences between control and high-dose groups, with an area under the curve ≥ 0.900 in receiver operating characteristic analysis. Increased levels of seven fatty acids (FAs; e.g., palmitic acid) and five fatty acyl esters of hydroxy FAs (e.g., FAHFA 22:6_22:5) were observed, suggesting roles in neurodegenerative diseases and inflammation. These findings identify a promising lipid biomarker linked to NN-induced neurotoxicity and contribute to detecting neurotoxic effects from acute exposure to such substances.

Monoamine neurotransmitters (MAs), including dopamine (DA) and serotonin (5-HT), regulate brain functions such as behavior, memory, and learning. Neonicotinoids are pesticides that are being used more frequently. Neonicotinoid exposure has been observed to produce neurological symptoms, such as altered spontaneous movements and anxiety-like behaviors, which are suspected to be caused by altered MA levels. However, current neurotoxicity tests are not sufficiently sensitive enough to make these determinations. In this study, we performed some behavior tests, and derivatization reagents to improve the ionization efficiency, which was applied to liquid chromatography mass spectrometry (LC-MS/MS) to reveal the effect of neonicotinoid administration on MAs in the brain. We orally administered the neonicotinoid imidacloprid (0, 10, and 50 mg/kg body weight) to C57BL/6NCrSlc mice. In the behavior tests, a decrease in activity was observed. The LC-MS/MS quantification of MAs in various brain regions showed a decrease in some MA levels in the olfactory bulb and the striatum. These results showed, for the first time, that even a low dose of imidacloprid could alter MA levels in various parts of the brain.

Monoamine neurotransmitters (MAs), including dopamine (DA) and serotonin (5-HT), regulate brain functions such as behavior, memory, and learning. Neonicotinoids are pesticides that are being used more frequently. Neonicotinoid exposure has been observed to produce neurological symptoms, such as altered spontaneous movements and anxiety-like behaviors, which are suspected to be caused by altered MA levels. However, current neurotoxicity tests are not sufficiently sensitive to make these determinations. In this study, we performed some behavior tests, and derivatization reagents to improve the ionization efficiency was applied to liquid chromatography mass spectrometry (LC/MS/MS) to reveal the effect of neonicotinoid administration on MAs in the brain.We orally administered the neonicotinoid imidacloprid (0, 10, and 50 mg/kg body weight) to C57BL/6NCrSlc mice. In behavior tests, the decrease of activity was observed. The LC/MS/MS quantification of MAs in various brain regions showed a decrease in some MA levels in the olfactory bulb and the striatum. These results showed for the first time that even low dose of imidacloprid could alter MA levels in various parts of the brain.