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Sub‐chronic administration of benzo[a]pyrene disrupts hippocampal long‐term potentiation via inhibiting CaMK II / PKC / PKA‐ERK‐CREB signaling in rats
Author(s) -
Lyu Yi,
Ren XueKe,
Zhang HuiFang,
Tian FengJie,
Mu JianBing,
Zheng JinPing
Publication year - 2020
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22932
Subject(s) - creb , neurotoxicity , long term potentiation , nmda receptor , benzo(a)pyrene , signal transduction , mapk/erk pathway , protein kinase c , chemistry , glutamate receptor , phosphorylation , hippocampal formation , microbiology and biotechnology , receptor , pharmacology , biology , endocrinology , medicine , transcription factor , biochemistry , toxicity , carcinogen , gene
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.