Northern Kentucky University

Spontaneous Alternation Behavior of AhrdCyp1a2(-/-) and AhrbCyp1a2(-/-) and AhrbCyp1a2(+/+) Mice Exposed to Polychlorinated Biphenyls During Gestation and Lactation

Institution

Northern Kentucky University

Abstract

Cytochrome P450 1A2 (CYP1A2) has been shown to play an important role in metabolizing some toxicants including polychlorinated biphenyls (PCBs). CYP1A2 upregulation is dependent on the relative binding affinity of the aryl hydrocarbon receptor (AHR) to a ligand, in our case coplanar PCBs. Previous work in our lab found learning and memory deficits in PCB-exposed Cyp1a2(-/-) mice compared to Cyp1a2(+/+) wild type mice. Both poor-affinity AhrdCyp1a2(-/- )and high-affinity Ahrb1Cyp1a2(-/-) mice had significant deficits in novel object recognition and Morris water maze tests compared with Ahrb1Cyp1a2(+/+) wild type mice. For this project, we modified our dosing protocol to provide an environmentally relevant mixture of PCBs in corn oil-soaked food daily to dams from gestational day 0 (GD0) to postnatal day 25 (PND 25). We tested spatial learning and working memory in the offspring at PND60 using the Y-maze test of spontaneous alternation. We found no significant differences in latency to leave the original arm, total number of arms entered, or percent alternation based on genotype or treatment (P>0.05). This suggests that the Y-maze is not as sensitive as the Morris water maze in detecting deficits in spatial learning and memory following developmental PCB exposure.

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Spontaneous Alternation Behavior of AhrdCyp1a2(-/-) and AhrbCyp1a2(-/-) and AhrbCyp1a2(+/+) Mice Exposed to Polychlorinated Biphenyls During Gestation and Lactation

Cytochrome P450 1A2 (CYP1A2) has been shown to play an important role in metabolizing some toxicants including polychlorinated biphenyls (PCBs). CYP1A2 upregulation is dependent on the relative binding affinity of the aryl hydrocarbon receptor (AHR) to a ligand, in our case coplanar PCBs. Previous work in our lab found learning and memory deficits in PCB-exposed Cyp1a2(-/-) mice compared to Cyp1a2(+/+) wild type mice. Both poor-affinity AhrdCyp1a2(-/- )and high-affinity Ahrb1Cyp1a2(-/-) mice had significant deficits in novel object recognition and Morris water maze tests compared with Ahrb1Cyp1a2(+/+) wild type mice. For this project, we modified our dosing protocol to provide an environmentally relevant mixture of PCBs in corn oil-soaked food daily to dams from gestational day 0 (GD0) to postnatal day 25 (PND 25). We tested spatial learning and working memory in the offspring at PND60 using the Y-maze test of spontaneous alternation. We found no significant differences in latency to leave the original arm, total number of arms entered, or percent alternation based on genotype or treatment (P>0.05). This suggests that the Y-maze is not as sensitive as the Morris water maze in detecting deficits in spatial learning and memory following developmental PCB exposure.