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.
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.
Abdel-Rahman
Ali
A
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Dechkovskaia
Anjelika M
AM
Mehta-Simmons
Heena
H
Sutton
Jazmine M
JM
Guan
Xiangrong
X
Khan
Wasiuddin A
WA
Abou-Donia
Mohamed B
MB
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001392:Azocines / Q000494:pharmacology; D002038:Bungarotoxins / Q000633:toxicity; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004390:Chlorpyrifos / Q000633:toxicity*; D002802:Cholinesterases / Q000097:blood; D004357:Drug Synergism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis* / Q000235:genetics; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D009538:Nicotine / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000633:toxicity*; D010276:Parasympatholytics / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011807:Quinolizines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D012741:Sexual Maturation; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D001392:Azocines; D002038:Bungarotoxins; D004390:Chlorpyrifos; D002802:Cholinesterases; D005904:Glial Fibrillary Acidic Protein; D007306:Insecticides; D009538:Nicotine; D018722:Nicotinic Agonists; D010276:Parasympatholytics; D010890:Pirenzepine; D011807:Quinolizines; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; C065959:AFDX 384; C004712:cytisine; D000093843:Quinolizidine Alkaloids