title: 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 longterm (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.
authors: Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan. J.KKURO.582@gmail.com.
authors: Junko
authors: J
authors: Kimura-Kuroda
authors: Center for Basic Technology Research, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan. nishito-ys@igakuken.or.jp.
authors: Yasumasa
authors: Y
authors: Nishito
authors: Advanced Clinical Research Center, Institute of Neurological Disorders, Kawasaki, Kanagawa 215-0026, Japan. hiro-yanagisawa@jikei.ac.jp.
authors: Hiroko
authors: H
authors: Yanagisawa
authors: Environmental Neuroscience Information Center, Musashino, Tokyo 180-0014, Japan. yo-kuroda@nifty.com.
authors: Yoichiro
authors: Y
authors: Kuroda
authors: Division of Neurology, Department of Internal Medicine, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan. con376@ndmc.ac.jp.
authors: Yukari
authors: Y
authors: Komuta
authors: Department of Health & Dietetics, Teikyo Heisei University, Toshima-ku, Tokyo 170-8445, Japan. kawano.hitoshi3@gmail.com.
authors: Hitoshi
authors: H
authors: Kawano
authors: Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan. hayashi-ms@igakuken.or.jp.
authors: Masaharu
authors: M
authors: Hayashi
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000187:drug effects* / Q000196:embryology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007093:Imidazoles / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D000073943:Neonicotinoids; D009474:Neurons / Q000187:drug effects*; D009538:Nicotine / Q000633:toxicity*; D009574:Nitro Compounds / Q000633:toxicity*; D011725:Pyridines / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000235:genetics; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D007093:Imidazoles; D007306:Insecticides; D000073943:Neonicotinoids; D009574:Nitro Compounds; D011725:Pyridines; D011978:Receptors, Nicotinic; C082359:imidacloprid; C464485:acetamiprid; D009538:Nicotine
keywords: acetamiprid; brain development; cerebellar culture; developmental neurotoxicity; imidacloprid; microarray; neonicotinoid; pesticide; transcriptome