title: Permanently compromised NADPH-diaphorase activity within the osmotically activated supraoptic nucleus after in utero but not adult exposure to Aroclor 1254.
abstract: Stimulated vasopressin (VP) release from magnocellular neuroendocrine cells in the supraoptic nucleus (SON) of hyperosmotic rats is inhibited by treatment with the industrial polychlorinated biphenyl (PCB) mixture, Aroclor 1254. Because VP responses to hyperosmotic stimulation are regulated by nitric oxide (NO) signaling, we studied NO synthase (NOS) activity in the SON of hyperosmotic rats as potential target of PCB-induced disruption of neuroendocrine processes necessary for osmoregulation. To examine PCB-induced changes in NOS activity under normosmotic and hyperosmotic conditions, male Sprague-Dawley rats were exposed to Aroclor 1254 (30mg/kg/day) in utero and NADPH-diaphorase (NADPH-d) activity was assessed in SON sections at three ages: postnatal day 10, early adult (3-5 months) or late adult (14-16 months). Hyperosmotic treatment increased mean NADPH-d staining density of oil hyperosmotic controls by 19.9% in early adults and 58% in late adulthood vs normosmotic controls. In utero exposure to PCBs reduced hyperosmotic-induced upregulation of NADPH-d activity to control levels in early adults and by 28% in late adults. Basal NADPH-d was reduced in postnatal rats. Rats receiving PCB exposure as early adults orally for 14 days displayed normal responses. Our findings show that developmental but not adult exposure to PCBs significantly reduces NOS responses to hyperosmolality in neuroendocrine cells. Moreover, reduced NADPH-d activity produced by in utero exposure persisted in stimulated late adult rats concomitant with reduced osmoregulatory capacity vs oil controls (375±9 vs 349±5mOsm/L). These findings suggest that developmental PCBs permanently compromise NOS signaling in the activated neuroendocrine hypothalamus with potential osmoregulatory consequences.
authors.affiliation: Environmental Toxicology Graduate Program, University of California, Riverside 92521, USA.
authors.forename: Cary Glenn
authors.initials: CG
authors.lastname: Coburn
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside 92521, USA.
authors.forename: Abena
authors.initials: A
authors.lastname: Watson-Siriboe
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside 92521, USA.
authors.forename: Borin
authors.initials: B
authors.lastname: Hou
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside 92521, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Cheetham
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside 92521, USA.
authors.forename: Elizabeth Rachel
authors.initials: ER
authors.lastname: Gillard
authors.affiliation: Department of Cell Biology and Neuroscience, University of California, Riverside 92521, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Lin
authors.affiliation: Departamento de Neuromorfologia, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría "Ramón de la Fuente Muñiz", Ave. México-Xochimilco 101, Col. San Lorenzo Huipulco, C.P. 14370 México, D.F., Mexico.
authors.forename: Martha
authors.initials: M
authors.lastname: León-Olea
authors.affiliation: Departamento de Neuromorfologia, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría "Ramón de la Fuente Muñiz", Ave. México-Xochimilco 101, Col. San Lorenzo Huipulco, C.P. 14370 México, D.F., Mexico.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Sánchez-Islas
authors.affiliation: Departamento de Neuromorfologia, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría "Ramón de la Fuente Muñiz", Ave. México-Xochimilco 101, Col. San Lorenzo Huipulco, C.P. 14370 México, D.F., Mexico.
authors.forename: Samuel
authors.initials: S
authors.lastname: Mucio-Ramírez
authors.affiliation: Environmental Toxicology Graduate Program, University of California, Riverside 92521, USA; Department of Cell Biology and Neuroscience, University of California, Riverside 92521, USA. Electronic address: mcur@ucr.edu.
authors.forename: Margarita Concepcion
authors.initials: MC
authors.lastname: Currás-Collazo
mesh_terms: D000818:Animals; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity*; D008297:Male; D009252:NADPH Dehydrogenase / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D064587:Osmoregulation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013495:Supraoptic Nucleus / Q000187:drug effects* / Q000201:enzymology*
chemical_list: D020111:Chlorodiphenyl (54% Chlorine); D052248:Nitric Oxide Synthase Type I; D009252:NADPH Dehydrogenase
keywords: Endocrine disrupting chemicals; Neurotoxicity; Nitric oxide; Persistent organic pollutants; Vasopressin