Abstract：
:Amitraz is a formamidine pesticide that has been reported to be a neurotoxic compound that induces convulsions among other effects. Excitatory and inhibitory neurotransmission is mediated mainly by glutamate and GABA, respectively, so their alteration could be responsible for induction of seizures. In this regard, amitraz α2 adrenergic agonist action, which has been suggested as likely responsible for this effect, could alter these neurotransmitter systems and lead to seizure induction. Moreover, other amitraz mechanisms such as histamine H1 receptor inhibition could be involved. To confirm if amitraz disrupts glutamatergic/GABAergic transmission by these mechanisms, we evaluated, in primary hippocampal neurons, the effect of amitraz (0.01 μM to 100 μM) with or without the α2 adrenergic antagonist idazoxan (1 μM) and/or the H1 receptor agonist n-methylhistaprodifen (30 μM) co-treatment on 4-aminobutyrate aminotransferase, glutamate decarboxylase 65 (GAD 65), succinate-semialdehyde dehydrogenase and glutaminase gene expression and on glutamate and GABA levels after 24h treatment. We observed that amitraz disrupts glutaminase and GAD 65 gene expression, altering glutamatergic and GABAergic transmission. These effects were mediated partially by H1 and α2 receptors suggesting that other mechanisms could be involved. These data could help explain the mechanism by which amitraz induces seizures and provide a therapeutic strategy to protect against this effect in case of poisoning.
journal_name
Neurotoxicol Teratoljournal_title
Neurotoxicology and teratologyauthors
Del Pino J,Frejo MT,Baselga MJ,Moyano P,Díaz MJdoi
10.1016/j.ntt.2015.06.007subject
Has Abstractpub_date
2015-07-01 00:00:00pages
82-7eissn
0892-0362issn
1872-9738pii
S0892-0362(15)30009-Xjournal_volume
50pub_type
杂志文章abstract：:With the implementation of the Food Quality Protection Act in 1996, more detailed evaluations of possible health effects of pesticides on developing organisms have been required. As a result, considerable developmental neurotoxicity (DNT) data have been generated on a variety of endpoints, including developmental chan...
journal_title：Neurotoxicology and teratology
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journal_title：Neurotoxicology and teratology
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journal_title：Neurotoxicology and teratology
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