Neonicotinoid Insecticides Alter the Gene Expression Profile of Neuron-Enriched Cultures from Neonatal Rat Cerebellum

Abstract

Neonicotinoids are considered safe because of their low affinities to mammalian nicotinic acetylcholine receptors (nAChRs) relative to insect nAChRs. However, because of importance of nAChRs in mammalian brain development, there remains a need to establish the safety of chronic neonicotinoid exposures with regards to children’s health. Here we examined the effects of long-term (14 days) and low dose (1 μM) exposure of neuron-enriched cultures from neonatal rat cerebellum to nicotine and two neonicotinoids: acetamiprid and imidacloprid. Immunocytochemistry revealed no differences in the number or morphology of immature neurons or glial cells in any group versus untreated control cultures. However, a slight disturbance in Purkinje cell dendritic arborization was observed in the exposed cultures. Next we performed transcriptome analysis on total RNAs using microarrays, and identified significant differential expression (p < 0.05, q < 0.05, ≥1.5 fold) between control cultures versus nicotine-, acetamiprid-, or imidacloprid-exposed cultures in 34, 48, and 67 genes, respectively. Common to all exposed groups were nine genes essential for neurodevelopment, suggesting that chronic neonicotinoid exposure alters the transcriptome of the developing mammalian brain in a similar way to nicotine exposure. Our results highlight the need for further careful investigations into the effects of neonicotinoids in the developing mammalian brain.

Caste‐ and pesticide‐specific effects of neonicotinoid pesticide exposure on gene expression in bumblebees

“…Some of the genes affected by clothianidin exposure in our study have also been affected by neonicotinoids or other pesticides in other studies and species. These include muscular genes such as troponin and calponin (Kimura‐Kuroda et al, ; Lewis, Szilagyi, Gehman, Dennis, & Jackson, ; Wang et al, ) and metabolic enzymes such as glucose dehydrogenase (Christen et al, ) and hexosaminidase D (Qi et al, ; Yang, Liu, Liu, Qu, & Qian, ). At a different level, cellular transport genes such as the ABC transport family (Dermauw & Van Leeuwen, ), one member of which was differentially expressed in our study, have been suggested to provide tolerance of neonicotinoids, such as imidacloprid, acetamiprid and thiacloprid, with greater mortality identified for neonicotinoid‐exposed honeybee larvae treated with an ABC inhibitor (Hawthorne & Dively, ).…”

LC-ESI/MS/MS analysis of neonicotinoids in urine of very low birth weight infants at birth

“…Acetamiprid has some lipophilicity (Log P ow is 0.8) and is not ionized at physiological pH [31], which suggests that it may be retained in the human body, even if its receptor action is weak. There is also some evidence to suggest that acetamiprid is toxic for neurological development [27, 59–61]. It has yet to be clarified whether neonicotinoids have neurological toxicity in infants, but the safety of acetamiprid should be reviewed based on the possibility that neonicotinoids may transfer to and accumulate in fetuses at a high rate.…”

An update of the Worldwide Integrated Assessment (WIA) on systemic insecticides. Part 2: impacts on organisms and ecosystems

“…Exposure to imidacloprid also altered the regulation of genes important in mammalian brain development (Kimura-Kuroda et al 2016).…”

“…Dosage could either be acute or chronic, the latter shown as /d (per day). All studies demonstrated deleterious effects at the given dosage, except those marked NE (no effect) Taxon and species Effect on: Imidacloprid Clothianidin Fipronil Source and detailed effect Mammal Rat, Rattus norvegicus Reproduction 38 mg/kg/d a 0.1 mg/kg/d (NE) b 0.03–3 mg/kg/d c a Lohiya et al 2016 ; increased zinc uptake in ovaries may affect synthesis of reproductive hormones b Udo et al 2014 ; no effect on gestation or reproductive quality c de Barros et al 2016; perinatal exposure led to reduction in sperm mobility, though no other effects on reproduction Rat, Rattus norvegicus Growth and development 30 mg/kg/d Chaguri et al 2016 ; reduced weight gain Rat, Rattus norvegicus Genotoxic 0.26 mg/L a 170 mg/kg b 24 mg/kg/d(NE) c a Kimura-Kuroda et al 2016 ; several genes essential for brain development were up or down regulated at these chronic low doses b Arslan et al 2016 ; sex-specific genotoxicity at LD 50 dose; males more prone to genotoxicity C Ozdemir et al 2014 ; no impact detected on expression of genes in the hippocampus Rat, Rattus norvegicus Cytotoxic 1.1, 4, 20, 20, 40 mg/kg/d a,b,c,d,e 170 mg/kg f 12 mg/kg/d g 5, 24, 30 mg/kg/d h,i,j 4.85 mg/kg/3.5d k 2.19, 10.9 mg/L l,m a Ibrahim et al 2015 ; disruption of thyroid hormone levels b Ozsahin et al 2014 ; biochemical alterations in kidneys c Kapoor et al 2014 ; increased levels of serum enzymes d Vohra et al 2014 ; marked changes to liver tissue and degeneration of hepatocytes e Annabi and Dhouib 2015 ; alteration of bioch...…”