Sub-chronic administration of benzo[a]pyrene disrupts hippocampal long-term potentiation via inhibiting CaMK II/PKC/PKA-ERK-CREB signaling in rats.
Environ Toxicol
; 35(9): 961-970, 2020 Sep.
Article
in En
| MEDLINE
| ID: mdl-32255272
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Benzo(a)pyrene
/
Protein Kinase C
/
Receptors, Glutamate
/
Receptors, N-Methyl-D-Aspartate
/
Long-Term Potentiation
/
CA1 Region, Hippocampal
Limits:
Animals
Language:
En
Journal:
Environ Toxicol
Journal subject:
SAUDE AMBIENTAL
/
TOXICOLOGIA
Year:
2020
Document type:
Article
Affiliation country: