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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

  • Developmental Toxicology
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Abstract.

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 (~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 (~134 and 126% of control, respectively) in AChE activity in the brainstem. No significant changes were observed in the ligand binding densities for α4β2 and α7 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.

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Acknowledgements.

The work was financially supported by the US EPA (EPA grant #R829399-01-0). The views, opinion and/or findings contained in this report are those of the authors and should not be construed as an official US EPA policy or decision unless so designated by other documents.

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Authors and Affiliations

  1. Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA

    Ali Abdel-Rahman, Anjelika M. Dechkovskaia, Heena Mehta-Simmons, Jazmine M. Sutton, Xiangrong Guan, Wasiuddin A. Khan & Mohamed B. Abou-Donia

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  1. Ali Abdel-Rahman
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  2. Anjelika M. Dechkovskaia
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Correspondence to Mohamed B. Abou-Donia.

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Abdel-Rahman, A., Dechkovskaia, A.M., Mehta-Simmons, H. et al. 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. Arch Toxicol 78, 467–476 (2004). https://doi.org/10.1007/s00204-004-0560-5

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