Sub‐chronic administration of benzo[a]pyrene disrupts hippocampal long‐term potentiation via inhibiting CaMK II / PKC / PKA‐ERK‐CREB signaling in rats

Benzo[a]pyrene (B[a]P) is recognized as a neurotoxic pollutant to mammals, which could impair learning and memory function. Although there is some evidence to suggest that N ‐methyl‐ d ‐aspartate receptor (NMDAR), a glutamate receptor and ion channel protein in nerve cells, is involved into the B[a]P induced neurotoxicity, the exact molecular mechanisms remain to be elucidated, particularly the effects of B[a]P on the NMDAR downstream signaling transduction pathways. In the present study, we examined the neurotoxicity of sub‐chronic administrated B[a]P on male Sprague‐Dawley rats. Our data suggested that B[a]P exposure caused significant deficits in learning and memory function and the impairment of hippocampal LTP in rats. Further mechanistic studies indicate that B[a]P‐induced learning and memory deficits are associated with the inhibition of NMDAR NR1 subunit transcription and protein phosphorylation. More importantly, the inactivation of CaMK II/PKC/PKA‐ERK‐CREB signaling pathways in hippocampus was detected at both the 2.5 and 6.25 mg/kg B[a]P‐treated groups, indicating that multiple targets in NMDAR and downstream signaling pathways are involved in the B[a]P‐induced neurotoxicity.