PMID- 36782369
OWN - NLM
STAT- MEDLINE
DCOM- 20230321
LR  - 20240216
IS  - 1096-0929 (Electronic)
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 192
IP  - 1
DP  - 2023 Mar 20
TI  - Aryl hydrocarbon receptor activation affects nitrergic neuronal survival and 
      delays intestinal motility in mice.
PG  - 117-128
LID - 10.1093/toxsci/kfad014 [doi]
AB  - Despite progress describing the effects of persistent organic pollutants (POPs) 
      on the central nervous system, the effect of POPs on enteric nervous system (ENS) 
      function remains underexplored. We studied the effects of 
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a POP, and a potent aryl hydrocarbon 
      receptor (AHR) ligand, on the ENS and intestinal motility in mice. C57Bl/6J mice 
      treated with TCDD (2.4 microg/kg body weight) for 8 weeks (once per week) exhibited 
      significant delay in intestinal motility as shown by reduced stool frequency, 
      prolonged intestinal transit time, and a persistence of dye in the jejunum 
      compared to control mice with maximal dye retention in the ileum. TCDD 
      significantly increased Cyp1a1 expression, an AHR target gene, and reduced the 
      total number of neurons and affected nitrergic neurons in cells isolated from WT 
      mice, but not Ahr-/- mice. In immortalized fetal enteric neuronal cells, 
      TCDD-induced nuclear translocation of AHR as well as increased Cyp1a1 expression. 
      AHR activation did not affect neuronal proliferation. However, AHR activation 
      resulted in enteric neuronal toxicity, specifically, nitrergic neurons. Our 
      results demonstrate that TCDD adversely affects nitrergic neurons and thereby 
      contributes to delayed intestinal motility. These findings suggest that AHR 
      signaling in the ENS may play a role in modulating TCDD-induced gastrointestinal 
      pathophysiology.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of the 
      Society of Toxicology. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Vijay, Anitha
AU  - Vijay A
AD  - Department of Veterinary and Biomedical Sciences, The Pennsylvania State 
      University, University Park, Pennsylvania 16802, USA.
FAU - Boyle, Nina R
AU  - Boyle NR
AD  - Department of Veterinary and Biomedical Sciences, The Pennsylvania State 
      University, University Park, Pennsylvania 16802, USA.
FAU - Kumar, Supriya M
AU  - Kumar SM
AD  - Department of Veterinary and Biomedical Sciences, The Pennsylvania State 
      University, University Park, Pennsylvania 16802, USA.
FAU - Perdew, Gary H
AU  - Perdew GH
AD  - Department of Veterinary and Biomedical Sciences, The Pennsylvania State 
      University, University Park, Pennsylvania 16802, USA.
FAU - Srinivasan, Shanthi
AU  - Srinivasan S
AD  - Department of Digestive Diseases, Emory University School of Medicine, Atlanta, 
      Georgia, USA.
AD  - Atlanta VA Medical Center, Decatur, Georgia, USA.
FAU - Patterson, Andrew D
AU  - Patterson AD
AUID- ORCID: 0000-0003-2073-0070
AD  - Department of Veterinary and Biomedical Sciences, The Pennsylvania State 
      University, University Park, Pennsylvania 16802, USA.
LA  - eng
GR  - R01 DK044234/DK/NIDDK NIH HHS/United States
GR  - R35 ES028244/ES/NIEHS NIH HHS/United States
GR  - R01 DK080684/DK/NIDDK NIH HHS/United States
GR  - R01 ES028288/ES/NIEHS NIH HHS/United States
GR  - S10 OD021750/OD/NIH HHS/United States
GR  - I01 BX000136/BX/BLRD VA/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Environmental Pollutants)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Receptors, Aryl Hydrocarbon/metabolism
MH  - Cytochrome P-450 CYP1A1/metabolism
MH  - *Nitrergic Neurons/metabolism
MH  - *Polychlorinated Dibenzodioxins/toxicity
MH  - *Environmental Pollutants
MH  - Mice, Inbred C57BL
PMC - PMC10025877
OTO - NOTNLM
OT  - AHR
OT  - ENS
OT  - TCDD
OT  - intestinal transit
OT  - nNOS
EDAT- 2023/02/15 06:00
MHDA- 2023/03/22 06:00
PMCR- 2024/02/14
CRDT- 2023/02/14 00:23
PHST- 2023/02/15 06:00 [pubmed]
PHST- 2023/03/22 06:00 [medline]
PHST- 2023/02/14 00:23 [entrez]
PHST- 2024/02/14 00:00 [pmc-release]
AID - 7035952 [pii]
AID - kfad014 [pii]
AID - 10.1093/toxsci/kfad014 [doi]
PST - ppublish
SO  - Toxicol Sci. 2023 Mar 20;192(1):117-128. doi: 10.1093/toxsci/kfad014.