No-observed-adverse-effect-level (NOAEL) clothianidin, a neonicotinoid pesticide, impairs hippocampal memory and motor learning associated with alteration of gene expression in cerebellum

Neonicotinoid pesticides (NNs) have been associated with numerous neurobehavioral effects in rodents, raising concerns about their impact on cognitive function. Clothianidin (CLO), a type of NN, was orally administered to male mice (10 weeks old, C57BL/6N) at the no-observed-adverse-effect level (NO...

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Bibliographic Details
Published in:Journal of Veterinary Medical Science 2024, Vol.86(3), pp.340-348
Main Authors: HARA, Yukako, SHODA, Asuka, YONOICHI, Sakura, ISHIDA, Yuya, MURATA, Midori, KIMURA, Mako, ITO, Makiko, NUNOBIKI, Sarika, YOSHIMOTO, Ayano, MANTANI, Youhei, YOKOYAMA, Toshifumi, HIRANO, Tetsushi, IKENAKA, Yoshinori, TABUCHI, Yoshiaki, HOSHI, Nobuhiko
Format: Article
Language:English
Subjects:
Animals
Cerebellum
Cognitive ability
DNA microarrays
Gene Expression
Guanidines
Hippocampus
Hippocampus - chemistry
Liquid chromatography
Locomotor activity
Male
Mass spectroscopy
Memory
Mice
Mice, Inbred C57BL
Monoamines
Motor skill learning
neonicotinoid
Neonicotinoids - toxicity
No-Observed-Adverse-Effect Level
novel location recognition test
Oral administration
Pesticides
Pesticides - analysis
Pesticides - metabolism
Risk assessment
rotarod test
Tandem Mass Spectrometry - veterinary
Thiazoles
Toxicology
Tryptamine
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Summary:Neonicotinoid pesticides (NNs) have been associated with numerous neurobehavioral effects in rodents, raising concerns about their impact on cognitive function. Clothianidin (CLO), a type of NN, was orally administered to male mice (10 weeks old, C57BL/6N) at the no-observed-adverse-effect level (NOAEL) of 50 mg/kg/day as indicated in the pesticide risk assessment report. Behavioral tests (novel location recognition and rotarod tests) evaluated hippocampal memory and cerebellar motor learning. After each test, plasma monoamines (3-methoxytyramine, histamine, serotonin, tryptamine) were measured by LC-ESI/MS/MS (Liquid chromatography-electrospray ionization/tandem mass spectrometry), and cerebellar mRNA expression was quantified by microarray and qRT-PCR analyses. The NOAEL of CLO was found to impair hippocampal memory, leading to decreased spontaneous locomotor activity and motor function. We reported, for the first time, multiple alterations of gene expression in the cerebellum associated with motor dysfunction.
ISSN:0916-7250
1347-7439
DOI:10.1292/jvms.23-0516