PMID- 15045467
OWN - NLM
STAT- MEDLINE
DCOM- 20050214
LR  - 20151119
IS  - 0340-5761 (Print)
IS  - 0340-5761 (Linking)
VI  - 78
IP  - 8
DP  - 2004 Aug
TI  - Maternal exposure to nicotine and chlorpyrifos, alone and in combination, leads 
      to persistently elevated expression of glial fibrillary acidic protein in the 
      cerebellum of the offspring in late puberty.
PG  - 467-76
AB  - We previously showed that maternal exposure to nicotine, alone or in combination 
      with chlorpyrifos, caused an increase in glial fibrillary acidic protein (GFAP) 
      immunostaining in the CA1 subfield of hippocampus and cerebellum in postnatal day 
      (PND) 30 offspring. In the present study, PND 60 offspring were evaluated for 
      histopathological and cholinergic effects following maternal exposure to nicotine 
      and chlorpyrifos, alone and in combination. Timed-pregnant Sprague-Dawley rats 
      (300-350 g) were treated daily with nicotine (1 mg/kg, s.c., in normal saline) or 
      chlorpyrifos (0.1 mg/kg, dermal, in ethanol) or a combination of nicotine and 
      chlorpyrifos from gestational days (GD) 4 to 20. Control animals were treated 
      with saline and ethanol. On PND 60, the offspring were evaluated for cholinergic 
      changes and pathological effects. Plasma butyrylcholinesterase (BChE) activity in 
      the female offspring from chlorpyrifos treated mothers showed a significant 
      increase (approximately 183% of control). Male offspring from mothers treated 
      with either chlorpyrifos or nicotine alone showed a significant increase in the 
      acetylcholinesterase (AChE) activity in the brainstem while female offspring from 
      mothers treated with either nicotine or a combination of nicotine and 
      chlorpyrifos showed a significant increase (approximately 134 and 126% of 
      control, respectively) in AChE activity in the brainstem. No significant changes 
      were observed in the ligand binding densities for alpha4beta2 and alpha7 
      nicotinic acetylcholine receptors in the cortex. Histopathological evaluation 
      using cresyl violet staining showed a significant decrease in surviving Purkinje 
      neurons in the cerebellum of the offspring from nicotine treated mothers. An 
      increase in GFAP immunostaining in cerebellar white matter was observed in the 
      offspring from the mothers treated with nicotine. These results suggest that 
      maternal exposure to real-life levels of nicotine and/or chlorpyrifos causes 
      differential regulation of brainstem AChE activity. Also, nicotine caused a 
      decrease in the surviving neurons and an increased expression of GFAP in 
      cerebellar white matter of the offspring on PND 60. These changes can lead to 
      long-term neurological adverse health effects later in life.
FAU - Abdel-Rahman, Ali
AU  - Abdel-Rahman A
AD  - Department of Pharmacology and Cancer Biology, Duke University Medical Center, 
      Durham, NC 27710, USA.
FAU - Dechkovskaia, Anjelika M
AU  - Dechkovskaia AM
FAU - Mehta-Simmons, Heena
AU  - Mehta-Simmons H
FAU - Sutton, Jazmine M
AU  - Sutton JM
FAU - Guan, Xiangrong
AU  - Guan X
FAU - Khan, Wasiuddin A
AU  - Khan WA
FAU - Abou-Donia, Mohamed B
AU  - Abou-Donia MB
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20040326
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (Alkaloids)
RN  - 0 (Azocines)
RN  - 0 (Bungarotoxins)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Insecticides)
RN  - 0 (Nicotinic Agonists)
RN  - 0 (Parasympatholytics)
RN  - 0 (Quinolizines)
RN  - 0 (Receptors, Muscarinic)
RN  - 0 (Receptors, Nicotinic)
RN  - 118290-27-0 (AFDX 384)
RN  - 3G0285N20N (Pirenzepine)
RN  - 53S5U404NU (cytisine)
RN  - 6M3C89ZY6R (Nicotine)
RN  - EC 3.1.1.8 (Cholinesterases)
RN  - JCS58I644W (Chlorpyrifos)
SB  - IM
MH  - Alkaloids/pharmacology
MH  - Animals
MH  - Azocines/pharmacology
MH  - Bungarotoxins/toxicity
MH  - Cerebellum/drug effects/*metabolism/pathology
MH  - Chlorpyrifos/*toxicity
MH  - Cholinesterases/blood
MH  - Drug Synergism
MH  - Female
MH  - Glial Fibrillary Acidic Protein/*biosynthesis/genetics
MH  - Insecticides/*toxicity
MH  - Male
MH  - Nicotine/*toxicity
MH  - Nicotinic Agonists/*toxicity
MH  - Parasympatholytics/pharmacology
MH  - Pirenzepine/*analogs & derivatives/pharmacology
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Quinolizines/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Muscarinic/drug effects
MH  - Receptors, Nicotinic/drug effects/metabolism
MH  - Sexual Maturation
EDAT- 2004/03/27 05:00
MHDA- 2005/02/16 09:00
CRDT- 2004/03/27 05:00
PHST- 2003/10/28 00:00 [received]
PHST- 2004/03/02 00:00 [accepted]
PHST- 2004/03/27 05:00 [pubmed]
PHST- 2005/02/16 09:00 [medline]
PHST- 2004/03/27 05:00 [entrez]
AID - 10.1007/s00204-004-0560-5 [doi]
PST - ppublish
SO  - Arch Toxicol. 2004 Aug;78(8):467-76. doi: 10.1007/s00204-004-0560-5. Epub 2004 
      Mar 26.