PMID- 32629208
OWN - NLM
STAT- MEDLINE
DCOM- 20200915
LR  - 20200915
IS  - 1873-6424 (Electronic)
IS  - 0269-7491 (Linking)
VI  - 266
IP  - Pt 1
DP  - 2020 Nov
TI  - Involvement of NMDAR/PSD-95/nNOS-NO-cGMP pathway in embryonic exposure to BPA 
      induced learning and memory dysfunction of rats.
PG  - 115055
LID - S0269-7491(20)31201-X [pii]
LID - 10.1016/j.envpol.2020.115055 [doi]
AB  - Bisphenol A (BPA), can lead to learning and memory impairment, but the underlying 
      mechanism is poorly understood. Researchers have indicated that the 
      N-methyl-D-aspartate receptor (NMDAR)/postsynaptic density protein 95 
      (PSD-95)/neuronal nitric oxide synthase (nNOS)-nitric oxide (NO)-cyclic guanosine 
      monophosphate (cGMP) pathway greatly contributes to learning and memory process. 
      Pregnant rats were exposed to 0, 0.05, 0.5, 5 and 50 mg/kg/day BPA via oral 
      gavage from gestational day (GD) 5 to GD 19. Morris water maze, transmission 
      electron microscope, western blot, real time PCR, biochemical analysis and ELISA 
      were used to analyze the changes in behavior, synaptic ultrastructure, protein 
      and gene expression of NMDAR, PSD-95, nNOS, together with nNOS activity, NO 
      (Nitrate reductase method) and cGMP levels of the rat pups at different growth 
      stages. Results of this research displayed that exposure to 0.5 mg/kg/day BPA 
      could damage the spatial learning ability of rats at postnatal day (PND) 56. 
      However, spatial memory ability could be affected by exposure to BPA at doses up 
      to 5 mg/kg/day. Moreover, the thickness of the postsynaptic density decreased 
      after exposure to BPA at doses of 5 and 50 mg/kg/day. Levels of NR1, NR2A, PSD-95 
      protein and mRNA were downregulated to some extent after exposure to BPA, whereas 
      the expression of NR2B increased at GD 20 but decreased at PND 21 and 56. 
      Contrarily, the nNOS expression along with the enzyme activity were promoted 
      after exposure to BPA. Meanwhile, the NO and cGMP levels were suppressed at GD 20 
      but promoted at PND 21 and 56. In conclusion, these results demonstrated that 
      NMDAR/PSD-95/nNOS-NO-cGMP pathway could be affected by embryonic exposure to BPA, 
      which may involve in the spatial learning and memory dysfunction of rats in later 
      life.
CI  - Copyright (c) 2020 Elsevier Ltd. All rights reserved.
FAU - Yu, Haiyang
AU  - Yu H
AD  - Department of Toxicology, School of Public Heath, Shenyang Medical College, 
      Shenyang, Liaoning Province, People's Republic of China. Electronic address: 
      yuhaiyang_edu@163.com.
FAU - Ma, Lin
AU  - Ma L
AD  - Department of Toxicology, School of Public Heath, Shenyang Medical College, 
      Shenyang, Liaoning Province, People's Republic of China.
FAU - Liu, Di
AU  - Liu D
AD  - Department of Toxicology, School of Public Heath, Shenyang Medical College, 
      Shenyang, Liaoning Province, People's Republic of China.
FAU - Wang, Yu
AU  - Wang Y
AD  - Department of Toxicology, School of Public Heath, Shenyang Medical College, 
      Shenyang, Liaoning Province, People's Republic of China.
FAU - Pei, Xiucong
AU  - Pei X
AD  - Department of Toxicology, School of Public Heath, Shenyang Medical College, 
      Shenyang, Liaoning Province, People's Republic of China.
FAU - Duan, Zhiwen
AU  - Duan Z
AD  - Department of Toxicology, School of Public Heath, Shenyang Medical College, 
      Shenyang, Liaoning Province, People's Republic of China.
FAU - Ma, Mingyue
AU  - Ma M
AD  - Department of Toxicology, School of Public Heath, Shenyang Medical College, 
      Shenyang, Liaoning Province, People's Republic of China.
FAU - Zhang, Yumin
AU  - Zhang Y
AD  - Department of Toxicology, School of Public Heath, Shenyang Medical College, 
      Shenyang, Liaoning Province, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20200629
PL  - England
TA  - Environ Pollut
JT  - Environmental pollution (Barking, Essex : 1987)
JID - 8804476
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Disks Large Homolog 4 Protein)
RN  - 0 (Phenols)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
RN  - MLT3645I99 (bisphenol A)
SB  - IM
MH  - Animals
MH  - Benzhydryl Compounds
MH  - Disks Large Homolog 4 Protein
MH  - Female
MH  - *Hippocampus
MH  - Nitric Oxide Synthase Type I
MH  - Phenols
MH  - Pregnancy
MH  - Rats
MH  - *Receptors, N-Methyl-D-Aspartate
OTO - NOTNLM
OT  - Bisphenol A
OT  - Learning and memory ability
OT  - NMDAR
OT  - PSD-95
OT  - nNOS
COIS- Declaration of competing interest The authors declare that they have no conflict 
      of interest.
EDAT- 2020/07/07 06:00
MHDA- 2020/09/17 06:00
CRDT- 2020/07/07 06:00
PHST- 2020/02/18 00:00 [received]
PHST- 2020/06/16 00:00 [revised]
PHST- 2020/06/16 00:00 [accepted]
PHST- 2020/07/07 06:00 [pubmed]
PHST- 2020/09/17 06:00 [medline]
PHST- 2020/07/07 06:00 [entrez]
AID - S0269-7491(20)31201-X [pii]
AID - 10.1016/j.envpol.2020.115055 [doi]
PST - ppublish
SO  - Environ Pollut. 2020 Nov;266(Pt 1):115055. doi: 10.1016/j.envpol.2020.115055. 
      Epub 2020 Jun 29.