PMID- 16482470
OWN - NLM
STAT- MEDLINE
DCOM- 20071029
LR  - 20151119
IS  - 0340-5761 (Print)
IS  - 0340-5761 (Linking)
VI  - 80
IP  - 9
DP  - 2006 Sep
TI  - In utero exposure to nicotine and chlorpyrifos alone, and in combination produces 
      persistent sensorimotor deficits and Purkinje neuron loss in the cerebellum of 
      adult offspring rats.
PG  - 620-31
AB  - This study was carried out to investigate the effect of in utero exposure to the 
      cholinotoxicants, nicotine and chlorpyrifos, alone or in combination on 
      neurobehavioral alterations and neuronal morphology latter in adult age. In the 
      present study, 90 days old (corresponding to a human adult age) male and female 
      offspring rats were evaluated for neurobehavioral, and neuropathological 
      alterations following maternal, gestational exposure to nicotine and chlorpyrifos 
      (O,O-diethyl-O-3,5,6-trichloro-2-pyridinyl phosphorothioate), alone and in 
      combination. Female Sprague-Dawley rats (300-350 g) with timed-pregnancy were 
      treated with nicotine (3.3 mg/kg/day, in bacteriostatic water via s.c. 
      implantation of mini osmotic pump), chlorpyrifos (1.0 mg/kg, daily, dermal, in 
      75% ethanol, 1.0 ml/kg) or a combination of both chemicals, on gestational days 
      (GD) 4-20. Control animals received bacteriostatic water via s.c. implantation of 
      mini osmotic pump and dermal application of 70% ethanol. The offspring at 
      postnatal day (PND) 90 were evaluated for neurobehavioral performance, changes in 
      the activity of plasma butyrylcholinesterase (BChE) and acetylcholinesterase 
      (AChE), and neuropathological alterations in the brain. Neurobehavioral 
      evaluations included beam-walk score, beam-walk time, incline plane performance 
      and forepaw grip time. Male and female offspring from mothers treated with 
      nicotine and CPF, alone or in combination showed impairments in the performance 
      of neurobehavioral tests, indicating sensorimotor deficits. Female offspring from 
      mothers treated with a combination of nicotine and chlorpyrifos showed 
      significant increase in plasma BChE activity. Brain regional AChE activity showed 
      differential increases in male and female offspring. Brainstem and cerebellum of 
      female offspring from mothers treated with nicotine or chlorpyrifos, alone or in 
      combination showed increased AChE activity, whereas brainstem of male offspring 
      from mothers treated with nicotine alone or a combination of nicotine and 
      chlorpyrifos showed increase in AChE activity. Also, male offspring exposed in 
      utero to nicotine exhibited increased AChE activity. Histopathological 
      evaluations using cresyl violet staining showed a decrease in surviving Purkinje 
      neurons in the cerebellum in offspring of all treatments groups. An increase in 
      glial fibrillary acidic protein (GFAP) immuno-staining was observed in cerebellum 
      white matter as well as granular cell layer (GCL) of cerebellum following all 
      exposures. These results indicate that in utero exposure to nicotine and 
      chlorpyrifos, alone and in combination produced significant sensorimotor deficits 
      in male and female offspring, differential increase in brain AChE activity, a 
      decrease in the surviving neurons and an increased expression of GFAP in 
      cerebellum in adult offspring rats at a corresponding human adult age. 
      Collectively, this study demonstrates that maternal exposure to environmental 
      neurotoxic chemicals, i.e., nicotine and chlorpyrifos leads to developmental 
      abnormalities in the offspring that persist latter into adulthood.
FAU - Abou-Donia, Mohamed B
AU  - Abou-Donia MB
AD  - Department of Pharmacology and Cancer Biology, Duke University Medical Center, 
      Durham, NC 27710, USA. donia@duke.edu
FAU - Khan, Wasiuddin A
AU  - Khan WA
FAU - Dechkovskaia, Anjelika M
AU  - Dechkovskaia AM
FAU - Goldstein, Larry B
AU  - Goldstein LB
FAU - Bullman, Sarah L
AU  - Bullman SL
FAU - Abdel-Rahman, Ali
AU  - Abdel-Rahman A
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20060216
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (Cholinesterase Inhibitors)
RN  - 6M3C89ZY6R (Nicotine)
RN  - EC 3.1.1.8 (Cholinesterases)
RN  - JCS58I644W (Chlorpyrifos)
SB  - IM
MH  - Administration, Topical
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Cell Death/drug effects
MH  - Chlorpyrifos/*toxicity
MH  - Cholinesterase Inhibitors/*toxicity
MH  - Cholinesterases/blood
MH  - Drug Therapy, Combination
MH  - Female
MH  - Infusion Pumps, Implantable
MH  - Injections, Subcutaneous
MH  - Male
MH  - Maternal Exposure/*adverse effects
MH  - Nicotine/*toxicity
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Psychomotor Performance/*drug effects
MH  - Purkinje Cells/*drug effects/pathology
MH  - Rats
EDAT- 2006/02/17 09:00
MHDA- 2007/10/30 09:00
CRDT- 2006/02/17 09:00
PHST- 2005/10/11 00:00 [received]
PHST- 2005/12/23 00:00 [accepted]
PHST- 2006/02/17 09:00 [pubmed]
PHST- 2007/10/30 09:00 [medline]
PHST- 2006/02/17 09:00 [entrez]
AID - 10.1007/s00204-006-0077-1 [doi]
PST - ppublish
SO  - Arch Toxicol. 2006 Sep;80(9):620-31. doi: 10.1007/s00204-006-0077-1. Epub 2006 
      Feb 16.