Bisphenol-A rapidly enhanced passive avoidance memory and phosphorylation of NMDA receptor subunits in hippocampus of young rats
Bisphenol-A (BPA), an endocrine disruptor, is found to influence development of brain and behaviors in rodents. The previous study indicated that perinatal exposure to BPA impaired learning-memory and inhibited N-methyl-D-aspartate receptor (NMDAR) subunits expressions in hippocampus during the postnatal development in rats; and in cultured hippocampal neurons, BPA rapidly promotes dynamic changes in dendritic morphology through estrogen receptor-mediated pathway by concomitant phosphorylation of NMDAR subunit NR2B. In the present study, we examined the rapid effect of BPA on passive avoidance memory and NMDAR in the developing hippocampus of Sprague-Dawley rats at the age of postnatal day 18. The results showed that BPA or estradiol benzoate (EB) rapidly extended the latency to step down from the platform 1 h after footshock and increased the phosphorylation levels of NR1, NR2B, and mitogen-activated extracellular signal-regulated kinase (ERK) in hippocampus within 1 h. While 24 h after BPA or EB treatment, the improved memory and the increased phosphorylation levels of NR1, NR2B, ERK disappeared. Furthermore, pre-treatment with an estrogen receptors (ERs) antagonist, ICI182,780, or an ERK-activating kinase inhibitor, U0126, significantly attenuated EB- or BPA-induced phosphorylations of NR1, NR2B, and ERK within 1 h. These data suggest that BPA rapidly enhanced short-term passive avoidance memory in the developing rats. A non-genomic effect via ERs may mediate the modulation of the phosphorylation of NMDAR subunits NR1 and NR2B through ERK signaling pathway. - Highlights: > BPA rapidly extended the latency to step down from platform 1 h after footshock. > BPA rapidly increased pNR1, pNR2B, and pERK in hippocampus within 1 h. > ERs antagonist or MEK inhibitor attenuated BPA-induced pNR1, pNR2B, and pERK.
- OSTI ID:
- 21587823
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 255, Issue 2; Other Information: DOI: 10.1016/j.taap.2011.06.022; PII: S0041-008X(11)00255-9; Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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ALBUMINS
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CALCIUM
CALMODULIN
CATTLE
ESTRADIOL
HIPPOCAMPUS
NERVE CELLS
PHOSPHORYLATION
RATS
RECEPTORS
SODIUM COMPOUNDS
SUBCUTANEOUS INJECTION
SULFURIC ACID ESTERS
ALKALI METAL COMPOUNDS
ALKALINE EARTH METALS
ANIMAL CELLS
ANIMALS
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BRAIN
CENTRAL NERVOUS SYSTEM
CHEMICAL REACTIONS
DOMESTIC ANIMALS
ELEMENTS
ESTERS
ESTRANES
ESTROGENS
HORMONES
HYDROXY COMPOUNDS
INJECTION
INTAKE
MAMMALS
MEMBRANE PROTEINS
METALS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PROTEINS
RODENTS
RUMINANTS
SOMATIC CELLS
STEROID HORMONES
STEROIDS
VERTEBRATES