Aging-related changes in the sensitivity of behavioral effects of the neonicotinoid pesticide clothianidin in male mice

Hirano, Tetsushi; Miyata, Yuka; Kubo, Shizuka; Ohno, Shuji; Onaru, Kanoko; Maeda, Mizuki; Kitauchi, Sayaka; Nishi, Misaki; Tabuchi, Yoshiaki; Ikenaka, Yoshinori; Ichise, Takahiro; Nakayama, Shouta M.M.; Ishizuka, Mayumi; Arizono, Koji; Takahashi, Keisuke; Kato, Kanefusa; Mantani, Youhei; Yokoyama, Toshifumi; Hoshi, Nobuhiko

doi:10.1016/j.toxlet.2021.02.010

Cited by 20 publications

(12 citation statements)

References 48 publications

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“…The toxic effects that NNs can produce in the brain depend on their ability to cross the BBB, which is the protection system that controls the exchange of endogenous and exogenous substances between the blood and the extracellular environment of the brain [56]. The studies analyzed confirmed that NNs do cross the BBB, based on the detection of pesticides and their metabolites in the brains of exposed animals [15,[57][58][59][60].…”

Section: Effects Of Nns On Rodentsmentioning

confidence: 84%

“…So, in the study by Hirano et al [58], after the administration of 5 mg/kg of CLO, variable concentrations of the pesticide and its metabolites were found in the brain. The levels detected in the brain reached values of 0.2 ppm in adult mice and almost 0.3 ppm in aged mice, approximately 5% of the total dose administered.…”

Section: Effects Of Nns On Rodentsmentioning

confidence: 97%

“…It has been shown that exposure to CLO or IMI during the gestational and lactation period was associated with various alterations in behavioral parameters in several generations of offspring [57,68,69]. Behavioral alterations were also observed in adolescent and adult rodents treated with IMI and CLO, in particular, deficits in motor behavior were described, especially in animals exposed to the highest doses of the pesticides [58,70,71].…”

Section: Effects On Behavior and Cognitive Functionsmentioning

confidence: 99%

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Neurotoxic Effects of Neonicotinoids on Mammals: What Is There beyond the Activation of Nicotinic Acetylcholine Receptors?—A Systematic Review

Costas-Ferreira

Faro

2021

IJMS

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Neonicotinoids are a class of insecticides that exert their effect through a specific action on neuronal nicotinic acetylcholine receptors (nAChRs). The success of these insecticides is due to this mechanism of action, since they act as potent agonists of insect nAChRs, presenting low affinity for vertebrate nAChRs, which reduces potential toxic risk and increases safety for non-target species. However, although neonicotinoids are considered safe, their presence in the environment could increase the risk of exposure and toxicity. On the other hand, although neonicotinoids have low affinity for mammalian nAChRs, the large quantity, variety, and ubiquity of these receptors, combined with its diversity of functions, raises the question of what effects these insecticides can produce in non-target species. In the present systematic review, we investigate the available evidence on the biochemical and behavioral effects of neonicotinoids on the mammalian nervous system. In general, exposure to neonicotinoids at an early age alters the correct neuronal development, with decreases in neurogenesis and alterations in migration, and induces neuroinflammation. In adulthood, neonicotinoids induce neurobehavioral toxicity, these effects being associated with their modulating action on nAChRs, with consequent neurochemical alterations. These alterations include decreased expression of nAChRs, modifications in acetylcholinesterase activity, and significant changes in the function of the nigrostriatal dopaminergic system. All these effects can lead to the activation of a series of intracellular signaling pathways that generate oxidative stress, neuroinflammation and, finally, neuronal death. Neonicotinoid-induced changes in nAChR function could be responsible for most of the effects observed in the different studies.

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Section: Effects Of Nns On Rodentsmentioning

confidence: 84%

Section: Effects Of Nns On Rodentsmentioning

confidence: 97%

Section: Effects On Behavior and Cognitive Functionsmentioning

confidence: 99%

See 1 more Smart Citation

Neurotoxic Effects of Neonicotinoids on Mammals: What Is There beyond the Activation of Nicotinic Acetylcholine Receptors?—A Systematic Review

Costas-Ferreira

Faro

2021

IJMS

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“…However, NNs were found to affect nAChR-mediated neuroexcitatory action in mammals [ 27 ]. Reproductive toxicity [ 22 , 28 , 48 , 58 ], cognitive/emotional alterations, and developmental neurotoxicity of NNs [ 17 , 18 , 19 , 21 , 32 , 45 , 46 , 59 ] were later reported, in addition to a systematic review [ 9 ] of NNs. nAChR is expressed widely in the nervous system and skeletal muscle as well as in immune cells [ 26 ] and regulates antigen presentation, cytokine production, and anti-inflammatory responses [ 38 , 60 ].…”

mentioning

confidence: 99%

Next-generation effects of fetal and lactational exposure to the neonicotinoid pesticide clothianidin on the immune system and gut microbiota

Murata

Shoda

KIMURA

et al. 2023

The Journal of Veterinary Medical Science

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Recently, the effects of exposure to clothianidin (CLO) on the thymus and gut microbiota have become clear, but no report has examined its next-generation impacts. Pregnant C57BL/6N mice were administered a no-observed-adverse-effect-level dose of CLO until weaning. We examined CLO's effects on the gut microbiota and immune organs of dams and their 3-and 10-week-old male offspring. CLO administration led to several alterations of the top 30 bacterial genera in the gut microbiota in dams and 3-week-old mice. Compared to controls, 10-week-old mice had more thymic Hassall's corpuscles, and both dams and 10-week-old mice had fewer macrophages. These results suggest that fetal and lactational CLO exposure may affect the immune system and gut microbiota of the next generation.

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“…Hence, the toxicity of the metabolites of CLO as well as imidacloprid is of concern. More recently, it has been shown to have neurobehavioral effects in mammals even below the no-observed-adverse-effect-level (NOAEL) doses [ 10 , 11 , 12 , 13 , 20 , 33 , 34 , 39 ]. In addition, a correlation has been found between pesticide use and an increase in developmental disorders such as autism and learning disabilities [ 3 , 27 ].…”

mentioning

confidence: 99%

Elucidation of the neurological effects of clothianidin exposure at the no-observed-adverse-effect level (NOAEL) using two-photon microscopy <i>in vivo</i> imaging

Nishi

Sugio

Hirano

et al. 2022

The Journal of Veterinary Medical Science

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Neonicotinoid pesticides (NNs) cause behavioral abnormalities in mammals, raising concerns about their effects on neural circuit activity. We herein examined the neurological effects of the NN clothianidin (CLO) by in vivo Ca 2+ imaging using two-photon microscopy. Mice were fed the no-observed-adverse-effect-level (NOAEL) dose of CLO for 2 weeks and their neuronal activity in the primary somatosensory cortex (S1) was observed weekly for 2 weeks. CLO exposure caused a sustained influx of Ca 2+ in neurons in the S1 2/3 layers, indicating hyperactivation of neurons. In addition, microarray gene expression analysis suggested the induction of neuroinflammation and changes in synaptic activity. These results demonstrate that exposure to the NOAEL dose of CLO can overactivate neurons and disrupt neuronal homeostasis.

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Aging-related changes in the sensitivity of behavioral effects of the neonicotinoid pesticide clothianidin in male mice

Cited by 20 publications

References 48 publications

Neurotoxic Effects of Neonicotinoids on Mammals: What Is There beyond the Activation of Nicotinic Acetylcholine Receptors?—A Systematic Review

Neurotoxic Effects of Neonicotinoids on Mammals: What Is There beyond the Activation of Nicotinic Acetylcholine Receptors?—A Systematic Review

Next-generation effects of fetal and lactational exposure to the neonicotinoid pesticide clothianidin on the immune system and gut microbiota

Elucidation of the neurological effects of clothianidin exposure at the no-observed-adverse-effect level (NOAEL) using two-photon microscopy <i>in vivo</i> imaging

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