The enteric nervous system of P2Y13 receptor null mice is resistant against high-fat-diet- and palmitic-acid-induced neuronal loss.
Voss, Ulrikke LU ; Turesson, Michelle Foldschak ; Robaye, Bernard ; Boeynaems, Jean-Marie ; Olde, Björn LU ; Erlinge, David LU
and Ekblad, Eva
LU
(2014)
In Purinergic Signalling
10(3).
p.455-464
- Abstract
- Gastrointestinal symptoms have a major impact on the quality of life and are becoming more prevalent in the western population. The enteric nervous system (ENS) is pivotal in regulating gastrointestinal functions. Purinergic neurotransmission conveys a range of short and long-term cellular effects. This study investigated the role of the ADP-sensitive P2Y13 receptor in lipid-induced enteric neuropathy. Littermate P2Y13 (+/+) and P2Y13 (-/-) mice were fed with either a normal diet (ND) or high-fat diet (HFD) for 6 months. The intestines were analysed for morphological changes as well as neuronal numbers and relative numbers of vasoactive intestinal peptide (VIP)- and neuronal nitric oxide synthase (nNOS)-containing neurons. Primary cultures... (More)
- Gastrointestinal symptoms have a major impact on the quality of life and are becoming more prevalent in the western population. The enteric nervous system (ENS) is pivotal in regulating gastrointestinal functions. Purinergic neurotransmission conveys a range of short and long-term cellular effects. This study investigated the role of the ADP-sensitive P2Y13 receptor in lipid-induced enteric neuropathy. Littermate P2Y13 (+/+) and P2Y13 (-/-) mice were fed with either a normal diet (ND) or high-fat diet (HFD) for 6 months. The intestines were analysed for morphological changes as well as neuronal numbers and relative numbers of vasoactive intestinal peptide (VIP)- and neuronal nitric oxide synthase (nNOS)-containing neurons. Primary cultures of myenteric neurons from the small intestine of P2Y13 (+/+) or P2Y13 (-/-) mice were exposed to palmitic acid (PA), the P2Y13 receptor agonist 2meSADP and the antagonist MRS2211. Neuronal survival and relative number of VIP-containing neurons were analysed. In P2Y13 (+/+), but not in P2Y13 (-/-) mice, HFD caused a significant loss of myenteric neurons in both ileum and colon. In colon, the relative numbers of VIP-containing submucous neurons were significantly lower in the P2Y13 (-/-) mice compared with P2Y13 (+/+) mice. The relative numbers of nNOS-containing submucous colonic neurons increased in P2Y13 (+/+) HFD mice. HFD also caused ileal mucosal thinning in P2Y13 (+/+) and P2Y13 (-/-) mice, compared to ND fed mice. In vitro PA exposure caused loss of myenteric neurons from P2Y13 (+/+) mice while neurons from P2Y13 (-/-) mice were unaffected. Presence of MRS2211 prevented PA-induced neuronal loss in cultures from P2Y13 (+/+) mice. 2meSADP caused no change in survival of cultured neurons. P2Y13 receptor activation is of crucial importance in mediating the HFD- and PA-induced myenteric neuronal loss in mice. In addition, the results indicate a constitutive activation of enteric neuronal apoptosis by way of P2Y13 receptor stimulation. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4335058
- author
- Voss, Ulrikke
LU
; Turesson, Michelle Foldschak
; Robaye, Bernard
; Boeynaems, Jean-Marie
; Olde, Björn
LU
; Erlinge, David
LU
and Ekblad, Eva
LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Purinergic Signalling
- volume
- 10
- issue
- 3
- pages
- 455 - 464
- publisher
- Springer
- external identifiers
-
- pmid:24510452
- wos:000341772500005
- pmid:24510452
- scopus:84893196271
- ISSN
- 1573-9546
- DOI
- 10.1007/s11302-014-9408-5
- language
- English
- LU publication?
- yes
- id
- d22f2b5a-b269-4dfb-897f-3c2b95a1efb6 (old id 4335058)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/24510452?dopt=Abstract
- date added to LUP
- 2016-04-01 10:53:16
- date last changed
- 2022-01-26 03:29:01
@article{d22f2b5a-b269-4dfb-897f-3c2b95a1efb6,
abstract = {{Gastrointestinal symptoms have a major impact on the quality of life and are becoming more prevalent in the western population. The enteric nervous system (ENS) is pivotal in regulating gastrointestinal functions. Purinergic neurotransmission conveys a range of short and long-term cellular effects. This study investigated the role of the ADP-sensitive P2Y13 receptor in lipid-induced enteric neuropathy. Littermate P2Y13 (+/+) and P2Y13 (-/-) mice were fed with either a normal diet (ND) or high-fat diet (HFD) for 6 months. The intestines were analysed for morphological changes as well as neuronal numbers and relative numbers of vasoactive intestinal peptide (VIP)- and neuronal nitric oxide synthase (nNOS)-containing neurons. Primary cultures of myenteric neurons from the small intestine of P2Y13 (+/+) or P2Y13 (-/-) mice were exposed to palmitic acid (PA), the P2Y13 receptor agonist 2meSADP and the antagonist MRS2211. Neuronal survival and relative number of VIP-containing neurons were analysed. In P2Y13 (+/+), but not in P2Y13 (-/-) mice, HFD caused a significant loss of myenteric neurons in both ileum and colon. In colon, the relative numbers of VIP-containing submucous neurons were significantly lower in the P2Y13 (-/-) mice compared with P2Y13 (+/+) mice. The relative numbers of nNOS-containing submucous colonic neurons increased in P2Y13 (+/+) HFD mice. HFD also caused ileal mucosal thinning in P2Y13 (+/+) and P2Y13 (-/-) mice, compared to ND fed mice. In vitro PA exposure caused loss of myenteric neurons from P2Y13 (+/+) mice while neurons from P2Y13 (-/-) mice were unaffected. Presence of MRS2211 prevented PA-induced neuronal loss in cultures from P2Y13 (+/+) mice. 2meSADP caused no change in survival of cultured neurons. P2Y13 receptor activation is of crucial importance in mediating the HFD- and PA-induced myenteric neuronal loss in mice. In addition, the results indicate a constitutive activation of enteric neuronal apoptosis by way of P2Y13 receptor stimulation.}},
author = {{Voss, Ulrikke and Turesson, Michelle Foldschak and Robaye, Bernard and Boeynaems, Jean-Marie and Olde, Björn and Erlinge, David and Ekblad, Eva}},
issn = {{1573-9546}},
language = {{eng}},
number = {{3}},
pages = {{455--464}},
publisher = {{Springer}},
series = {{Purinergic Signalling}},
title = {{The enteric nervous system of P2Y13 receptor null mice is resistant against high-fat-diet- and palmitic-acid-induced neuronal loss.}},
url = {{https://lup.lub.lu.se/search/files/2209301/4692918.pdf}},
doi = {{10.1007/s11302-014-9408-5}},
volume = {{10}},
year = {{2014}},
}