Effects of lactational exposure to benzo[alpha]pyrene (B[alpha]P) on postnatal neurodevelopment, neuronal receptor gene expression and behaviour in mice.
The harmful effects of exposure to benzo[alpha]pyrene (B[alpha]P), which is a neurotoxic pollutant, on mammalian neurodevelopment and/or behaviour as yet remain widely unclear. In the present investigation, we evaluated the impact of the lactational exposure to B[alpha]P on postnatal development of pups and behaviour of young mice. The neurobiological effects of B[alpha]P during lactation were also evaluated on pups' brain. Here, we found that lactational exposure to B[alpha]P at 2 and 20mg/kg affects the neuromaturation of pups by significantly decreasing their reflex as highlighted in surface righting reflex and negative geotaxis tests. However, we noted a significant increase in muscular strength of lactationally B[alpha]P mg/kg-exposed pups, which was probably due to the impact of the exposure to this toxic compound on body weight gain. At the pup stage, lactational exposure to B[alpha]P also provoked a neurobiological change, which was assessed by determination of neuronal receptor gene expression. Indeed, a significant reduction in gene expression of 5HT(1A) receptors in pups exposed to B[alpha]P through lactation was found in comparison to controls. Additionally, attenuation in the expression of MOR(1) mRNA was observed, but statistically significant only in animals receiving the higher dose. Neither the expression levels of ADRA(1D) nor GABA(A) mRNA were altered. Interestingly, the harmful effects of lactational exposure to B[alpha]P on behaviour and cognitive function were still found despite a long post-weaning period. Young mice whose mothers were exposed to B[alpha]P displayed a disinhibition behaviour towards the aversive spaces of the elevated plus maze. Furthermore, a significant increase of spontaneous alternation in the Y-maze was observed, but only in young mice whose mothers were orally exposed to the lower dose of B[alpha]P. Our results suggest a close link between the neurobiological change highlighted in pups' brain and the different behavioural disturbances observed during postnatal development period until young adult stage.
Neurotoxicologie Alimentaire et Bioactivié, UR AFPA, Université Paul Verlaine de Metz-INPL-INRA, BP 4102, 57040 Metz, France. bouayedj@yahoo.fr
Jaouad
J
Bouayed
Frédéric
F
Desor
Hassan
H
Rammal
Alexandra K
AK
Kiemer
Elisabeth
E
Tybl
Henri
H
Schroeder
Guido
G
Rychen
Rachid
R
Soulimani
D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000139:chemically induced; D001522:Behavior, Animal / Q000187:drug effects*; D001564:Benzo(a)pyrene / Q000493:pharmacokinetics / Q000633:toxicity*; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D004785:Environmental Pollutants / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D007774:Lactation; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D008568:Memory / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011897:Random Allocation; D018340:Receptors, Adrenergic, alpha-1 / Q000096:biosynthesis / Q000235:genetics; D011963:Receptors, GABA-A / Q000096:biosynthesis / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000096:biosynthesis / Q000235:genetics; D011985:Receptors, Serotonin / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
C547720:Adra1d protein, mouse; D004785:Environmental Pollutants; D018340:Receptors, Adrenergic, alpha-1; D011963:Receptors, GABA-A; D017450:Receptors, Opioid, mu; D011985:Receptors, Serotonin; D001564:Benzo(a)pyrene