Alterations in nitric oxide synthase-expressing neurons in the forebrain regions of rats after developmental exposure to organophosphates

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• 作者：Maryam Naseh^a ; Jafar Vatanparast^a ; ^{vatanparast@shirazu.ac.ir} ; Mansoureh Baniasadi^a ; Gholam Ali Hamidi^b
• 关键词：AChE ; acetylcholinesterase ; CPF ; chlorpyrifos ; DMSO ; dimethylsulfoxide ; DZN ; diazinon ; GD ; gestational day ; NADPH-d ; nicotinamide adenine dinucleotide phosphate-diaphorase ; NO ; nitric oxide ; NOS ; nitric oxide synthase ; nNOS-IR ; neuronal NOS-immunoreactive
• 刊名：Neurotoxicology and Teratology
• 出版年：2013
• 出版时间：May-June, 2013
• 年：2013
• 卷：37
• 期：Complete
• 页码：23-32
• 全文大小：1512 K

文摘

Several mechanisms have been addressed as contributors to the long lasting behavioral deficits after developmental exposure to organophosphate (OP) compounds. Here, the effects of developmental exposure to two common OP insecticides, chlorpyrifos (CPF) and diazinon (DZN), on nitric oxide synthase (NOS)-expressing neurons in the rat forebrain are reported. A daily dose of 1 mg/kg of either CPF or DZN was administered to rats during gestational days 15-18 or postnatal days (PND) 1-4. We then assessed NADPH-diaphorase and neuronal NOS (nNOS) immunohistochemistry in forebrain sections on different postnatal days. Prenatal exposure to CPF and DZN induced a transient reduction of NADPH-d⁺/nNOS-immunoreactive (IR) neurons in most cortical regions on PND 4 but exceptionally increased them in the entorhinal/piriform cortex. On PND 15, NADPH-d⁺/nNOS-IR neurons showed morphological abnormalities within entorhinal/piriform cortex of the rats that gestationally exposed to CPF. Postnatal exposure to CPF and DZN did not induce widespread effects on the number of NADPH-d⁺/nNOS-IR neurons on PNDs 7 and 15 but significantly reduced them in most cortical regions and hippocampal subfields on PND 60. The OPs affected NADPH-d⁺/nNOS-IR neurons in a sex independent manner and apparently spared them in the striatum. While the NADPH-d reactivity of microvessels was normally diminished by age, OP treated rats evidently preserved the NADPH-d reactivity of microvessels in the cerebral cortex and hippocampus. The effects of OPs on NADPH-d⁺/nNOS-IR neurons may contribute to the long-lasting behavioral outcomes and expand the neurotransmitter system that need to be considered in OP neurotoxicity evaluations.