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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)
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organization
publishing date
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
  • scopus:84912112857
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
2014-03-06 13:35:21
date last changed
2017-05-28 03:20:36
@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          = {http://dx.doi.org/10.1007/s11302-014-9408-5},
  volume       = {10},
  year         = {2014},
}