Learning and memory retention deficits in prepubertal guinea pigs prenatally exposed to low levels of the organophosphorus insecticide malathion.
Learning and memory retention deficits in prepubertal guinea pigs prenatally exposed to low levels of the organophosphorus insecticide malathion.
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DOI：
10.1016/j.ntt.2020.106914
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发表时间：
2020-09
影响因子：
2.9
通讯作者：
Pereira EFR
中科院分区：
文献类型：
--
作者：
Lumsden EW;McCowan L;Pescrille JD;Fawcett WP;Chen H;Albuquerque EX;Mamczarz J;Pereira EFR
马拉硫磷是一种有机磷杀虫剂，广泛应用于农业、住宅环境和全球公共卫生项目，高剂量马拉硫磷可诱导乙酰胆碱酯酶（AChE）抑制产生明确的毒蛋白。然而，产前暴露于低于乙酰胆碱酯酶抑制阈值的马拉硫磷水平与神经发育障碍的风险增加有关，包括自闭症谱系障碍伴智力残疾合并症。本研究测试的假设，产前暴露于非乙酰胆碱酯酶抑制剂量的马拉硫磷是因果关系的性别偏见的认知缺陷，后来在生活中早熟的物种。为此，在妊娠第53天至第63天期间，对妊娠豚鼠皮下注射马拉硫磷（20 mg/kg）或溶剂（花生油，0.5 ml/kg），每日一次。这种马拉硫磷给药方案在母鼠和后代的大脑或血液中没有引起显着的乙酰胆碱酯酶抑制，对后代的出生后生长没有显着影响。出生后第30天左右，马拉硫磷和花生油暴露的后代之间的自发活动和习惯化，一种形式的非联想学习，是可比的。然而，在Morris水迷宫中，暴露于马拉硫磷的后代除了记忆障碍外，还表现出显着的性别依赖性空间学习障碍。这些结果意义深远，因为它们表明：（i）马拉硫磷是一种发育神经毒物，（ii）乙酰胆碱酯酶抑制不是一种适当的生物标志物，无法得出妊娠期间马拉硫磷暴露的安全限值。有必要继续开展研究，以确定马拉硫磷对发育神经的毒性的时间和剂量依赖性，以及这种杀虫剂对发育中的大脑产生有害影响的机制。
High doses of malathion, an organophosphorus (OP) insecticide ubiquitously used in agriculture, residential settings, and public health programs worldwide, induce a well-defined toxidrome that results from the inhibition of acetylcholinesterase (AChE). However, prenatal exposures to malathion levels that are below the threshold for AChE inhibition have been associated with increased risks of neurodevelopmental disorders, including autism spectrum disorder with intellectual disability comorbidity. The present study tested the hypothesis that prenatal exposures to a non-AChE-inhibiting dose of malathion are causally related to sex-biased cognitive deficits later in life in a precocial species. To this end, pregnant guinea pigs were injected subcutaneously with malathion (20 mg/kg) or vehicle (peanut oil, 0.5 ml/kg) once daily between approximate gestational days 53 and 63. This malathion dose regimen caused no significant AChE inhibition in the brain or blood of dams and offspring and had no significant effect on the postnatal growth of the offspring. Around postnatal day 30, locomotor activity and habituation, a form of non-associative learning, were comparable between malathion- and peanut oil-exposed offspring. However, in the Morris water maze, malathion-exposed offspring presented significant sexdependent spatial learning deficits in addition to memory impairments. These results are far-reaching as they indicate that: (i) malathion is a developmental neurotoxicant and (ii) AChE inhibition is not an adequate biomarker to derive safety limits of malathion exposures during gestation. Continued studies are necessary to identify the time and dose dependence of the developmental neurotoxicity of malathion and the mechanisms underlying the detrimental effects of this insecticide in the developing brain.
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影响因子：
10.4
作者：
Gunier RB;Bradman A;Harley KG;Kogut K;Eskenazi B
通讯作者：
Eskenazi B
影响因子：
4.7
作者：
Burke RD;Todd SW;Lumsden E;Mullins RJ;Mamczarz J;Fawcett WP;Gullapalli RP;Randall WR;Pereira EFR;Albuquerque EX
通讯作者：
Albuquerque EX
影响因子：
56.9
作者：
MEANEY, MJ;AITKEN, DH;SAPOLSKY, RM
通讯作者：
SAPOLSKY, RM
影响因子：
3.4
作者：
Mamczarz, Jacek;Pescrille, Joseph D.;Albuquerque, Edson X.
通讯作者：
Albuquerque, Edson X.
DOI：
10.1016/s0165-3806(01)00215-2
发表时间：
2001-09-23
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
Levin, ED;Addy, N;Slotkin, TA
通讯作者：
Slotkin, TA