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Titolo:
Developmental methylmercury administration alters cerebellar PSA-NCAM expression and Golgi sialyltransferase activity
Autore:
Dey, PM; Gochfeld, M; Reuhl, KR;
Indirizzi:
Rutgers State Univ, Coll Pharm, Dept Pharmacol & Toxicol, Neurotoxicol Labs, Piscataway, NJ 08854 USA Rutgers State Univ Piscataway NJ USA 08854 Labs, Piscataway, NJ 08854 USA Rutgers State Univ, UMDNJ RWJMS, Joint Grad Program Toxicol, Piscataway, NJ USA Rutgers State Univ Piscataway NJ USA Program Toxicol, Piscataway, NJ USA Environm & Occupat Hlth Sci Inst, Piscataway, NJ USA Environm & Occupat Hlth Sci Inst Piscataway NJ USA t, Piscataway, NJ USA
Titolo Testata:
BRAIN RESEARCH
fascicolo: 2, volume: 845, anno: 1999,
pagine: 139 - 151
SICI:
0006-8993(19991023)845:2<139:DMAACP>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL-ADHESION MOLECULE; CATECHOLAMINE NEUROTRANSMITTER SYSTEMS; DEVELOPING RAT-BRAIN; N-CAM; POLYSIALIC ACID; NERVOUS-SYSTEM; NEURONAL MIGRATION; SIALYLATION STATE; ADULT CONVERSION; CEREBRAL-CORTEX;
Keywords:
methylmercury; sialyltransferase; cerebellum; neural tell adhesion molecule; development; polysialylation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
90
Recensione:
Indirizzi per estratti:
Indirizzo: Reuhl, KR Rutgers State Univ, Coll Pharm, Dept Pharmacol & Toxicol, Neurotoxicol Labs, 41B Gordon Rd, Piscataway, NJ 08854 USA Rutgers State Univ 41BGordon Rd Piscataway NJ USA 08854 854 USA
Citazione:
P.M. Dey et al., "Developmental methylmercury administration alters cerebellar PSA-NCAM expression and Golgi sialyltransferase activity", BRAIN RES, 845(2), 1999, pp. 139-151

Abstract

Brain dysmorphogenesis and persistent psychomotor disturbances are hallmarks of developmental methylmercury (MeHg) exposure, but the molecular mechanisms underlying these effects are poorly understood. Targets of developmental MeHg exposure include neural cell adhesion molecules (NCAMs), sialoglycoconjugate molecules whose proper temporal and spatial expression is important at all stages of neurodevelopment and especially during synaptic structuring. To investigate the effects of MeHg on the temporal expression of NCAMduring development, rat pups were dosed with 7.0 mg/kg MeHgCl (s.c.) on alternate days from postnatal days (PNDs) 3-13 and killed on PNDs 15, 30 and 60. Brain MeHg concentrations were determined in a subset of litters injected with (CH3Hg)-Hg-203. Expression of NCAM180 protein and of NCAM180 polysialylation was examined in whole cerebellum homogenates, cerebellar synaptosomes and isolated cerebellar growth cones by Western blotting and immunocytochemical staining. NCAM sialyltransferase activity was assayed in preparations of purified Golgi apparatus from the cerebelli of rats treated in vivo, or following in vitro incubation with 0, 1, 2.5, or 7.5 mu M MeHg for 2 h. At PND15, no change in NCAM180 protein expression was observed in any cerebellar preparations, but decreased polysialylation of NCAM180 was observedin cerebellar whole homogenates, synaptosomes and isolated growth cones. At PND30, both NCAM180 protein expression and NCAM180 polysialylation were elevated in whole homogenate preparations but not in synaptosomes. NCAM180 expression in MeHg-treated rats was similar to controls at PND60, 47 days after the last methylmercury administration. In vivo studies of cerebellar Golgi sialyltransferase activity revealed significant reductions in PND15 MeHg-treated rats as compared to controls, but no changes in sialyltransferaseactivity in PND30 and PND60 animals. In vitro experiments revealed decreasing sensitivity of cerebellar sialyltransferases to MeHg as the developmental age of the rat increased. Toxic perturbation of the developmentally-regulated expression of polysialylated NCAM during brain formation may disturb the stereotypic formation of neuronal contacts and could contribute to the behavioral and morphological disturbances observed following MeHg poisoning. (C) 1999 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 19:11:43