PMID- 17618726
OWN - NLM
STAT- MEDLINE
DCOM- 20071016
LR  - 20151119
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 238
IP  - 1
DP  - 2007 Aug 16
TI  - Perinatal co-exposure to methylmercury and PCB153 or PCB126 in rats alters the 
      cerebral cholinergic muscarinic receptors at weaning and puberty.
PG  - 34-48
AB  - In the last few decades, combined exposure to methylmercury (MeHg) and 
      polychlorinated biphenyls (PCBs) from fish and seafood, and their potentially 
      interactive effects on neurodevelopment, have been giving increasing cause for 
      concern. We examined the combined effects of MeHg and either a non-dioxin PCB 
      (PCB153) or a dioxin-like PCB (PCB126) congener on the developing brain 
      cholinergic muscarinic receptors (MRs). These receptors are known to play a major 
      role in many central functions including higher cognitive processes and the 
      modulation of extrapyramidal motor activity. MRs in pup rat brains diminished 
      following prenatal and lactational exposure, from gestational day [GD]7 to 
      postnatal day [PND]21, to MeHg (0.5mg/kgbodyweight[bw]/day), PCB153 
      (5mg/kgbw/day), and PCB126 (100ng/kg/day), alone or in combination. Total MR 
      density, as well as M1, M2, and M3 receptor subtypes of the weanling and pubertal 
      rats, were affected in a brain-area-, gender-, time- and compound-dependent 
      fashion. MeHg decreased (by 15-20%) the total MR density in a delayed (PND36) 
      manner in the cerebral cortex of both genders, and early (at weaning) in the 
      cerebellum of both genders, with the effect lasting until puberty (in males 
      only). MeHg decreased the ACh M1- and M3-immunopositive neurons in the cerebral 
      cortex and also increased the M2-immunopositive Bergmann glia in the cerebellum. 
      PCB153 also induced a delayed (PND36) decrease (of 20%) in total MR number in the 
      cerebellum of the male offspring and in the cerebral cortex of both genders. The 
      latter effect was coupled with a decrease in ACh M1- and ACh M3-immunopositive 
      neuron populations. PCB126 decreased (by 30-40%) total MR density in a 
      gender-dependent manner, males being more sensitive than females. The effect was 
      evident early (at PND21) and lasted until puberty in the cerebellum, while it was 
      observed later (at PND36) in the cerebral cortex. The M1 and M3 receptors were 
      similarly affected by PCB126. Co-exposure to MeHg and either PCB153 or PCB126 had 
      the same effect on the cerebral MRs as exposure to each compound alone. The 
      results rule out additive or synergistic interactions between MeHg and PCB153 or 
      PCB126 on MRs in the brain areas examined. Some early-onset changes persisted 
      until puberty, while other modifications became manifest only at the advanced 
      time point (PND36), when the brain levels of total Hg, PCB153, and PCB126 had 
      declined. These data support the ability of MeHg and PCBs to induce delayed 
      neurotoxicity after developmental exposure.
FAU - Coccini, Teresa
AU  - Coccini T
AD  - IRCCS Salvatore Maugeri Foundation, Toxicology Division, Institute of Pavia, 
      Italy. tcoccini@fsm.it
FAU - Roda, Elisa
AU  - Roda E
FAU - Castoldi, Anna F
AU  - Castoldi AF
FAU - Goldoni, Matteo
AU  - Goldoni M
FAU - Poli, Diana
AU  - Poli D
FAU - Bernocchi, Graziella
AU  - Bernocchi G
FAU - Manzo, Luigi
AU  - Manzo L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070525
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Methylmercury Compounds)
RN  - 0 (Receptors, Muscarinic)
RN  - 10028-17-8 (Tritium)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - EZ74BDI0HB (methylmercury hydroxide)
RN  - TSH69IA9XF (3,4,5,3',4'-pentachlorobiphenyl)
RN  - ZRU0C9E32O (2,4,5,2',4',5'-hexachlorobiphenyl)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Cerebellum/drug effects/metabolism
MH  - Cerebral Cortex/*drug effects/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Immunohistochemistry
MH  - Male
MH  - Methylmercury Compounds/administration & dosage/*toxicity
MH  - Polychlorinated Biphenyls/administration & dosage/*toxicity
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects
MH  - Purkinje Cells/drug effects/metabolism
MH  - Pyramidal Cells/drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Muscarinic/*metabolism
MH  - Sex Factors
MH  - Time Factors
MH  - Tritium
MH  - Weaning
MH  - Weight Gain/drug effects
EDAT- 2007/07/10 09:00
MHDA- 2007/10/17 09:00
CRDT- 2007/07/10 09:00
PHST- 2007/04/02 00:00 [received]
PHST- 2007/05/10 00:00 [revised]
PHST- 2007/05/14 00:00 [accepted]
PHST- 2007/07/10 09:00 [pubmed]
PHST- 2007/10/17 09:00 [medline]
PHST- 2007/07/10 09:00 [entrez]
AID - S0300-483X(07)00299-5 [pii]
AID - 10.1016/j.tox.2007.05.018 [doi]
PST - ppublish
SO  - Toxicology. 2007 Aug 16;238(1):34-48. doi: 10.1016/j.tox.2007.05.018. Epub 2007 
      May 25.