title: Enhanced expression of hypothalamic nitric oxide synthase in rats developmentally exposed to organophosphates.
abstract: Nitric oxide synthase (NOS) is highly expressed in the hypothalamus, and nitric oxide (NO) specifically contributes to the regulation of neuronal activity within distinct hypothalamic regions. We studied the long-lasting effects of developmental exposure to low doses of organophosphate chlorpyrifos (CPF) and diazinon (DZN) on the expression of NOS in the hypothalamic subnuclei that subserve neuroendocrine, autonomic and cognitive functions. A daily dose of 1 mg/kg of either CPF or DZN was administered to developing rats during gestational days 15-18 or postnatal days (PND) 1-4. Brain sections from PND 60 rats were processed using NADPH-diaphorase (NADPH-d) and neuronal NOS (nNOS) immunohistochemistry. The number of labeled neurons and the optical density (OD) were assessed in the supraoptic (SON), paraventricular (PVN), medial septum, vertical limb, and horizontal limb of the diagonal band. Developmental exposure to organophosphates increased the number of labeled neurons and OD in different subnuclei in the hypothalamus without gender selectivity. The effect on OD was more pronounced and was significant for more cases. Prenatal exposure to CPF and DZN significantly increased the OD in all regions studied with the exception of PVN. Neonatal exposure to DZN also consistently increased OD in all studied subnuclei. For rats that treated with CPF during early postnatal period, this effect was statistically significant only for the SON and PVN. These findings suggest that overexpression of NOS in the hypothalamus may contribute to the mechanisms inducing or compensating for endocrine, autonomic and cognitive abnormalities after developmental exposure to organophosphates.
authors: Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran; Department of Physiology, Shiraz University of Medical Sciences, Shiraz, Iran.
authors: Maryam
authors: M
authors: Naseh
authors: Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran. Electronic address: jvatanparast@gmail.com.
authors: Jafar
authors: J
authors: Vatanparast
mesh_terms: D000818:Animals; D002452:Cell Count; D004390:Chlorpyrifos / Q000494:pharmacology*; D003976:Diazinon / Q000494:pharmacology*; D005260:Female; D007031:Hypothalamus / Q000187:drug effects* / Q000201:enzymology*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000201:enzymology; D051381:Rats
chemical_list: D019001:Nitric Oxide Synthase; D004390:Chlorpyrifos; D003976:Diazinon
keywords: Development; Medial septum/diagonal band; Nitric oxide synthase; Organophosphate; Paraventricular; Supraoptic