The enteric nervous system of P2Y13 receptor null mice is resistant against high-fat-diet- and palmitic-acid-induced neuronal loss.

Summary, in English

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.

• Författare: Ulrikke Voss; Michelle Foldschak Turesson; Bernard Robaye; Jean-Marie Boeynaems; Björn Olde; David Erlinge; Eva Ekblad
• Avdelning/ar: Neurogastroenterology; Kardiologi
• Publiceringsår: 2014
• Språk: Engelska
• Sidor: 455-464
• Publikation/Tidskrift/Serie: Purinergic Signalling
• Volym: 10
• Issue: 3
• Fulltext: - 4 MB; Download statistics
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/24510452?dopt=Abstract; http://dx.doi.org/10.1007/s11302-014-9408-5
• Dokumenttyp: Artikel i tidskrift
• Förlag: Springer
• Ämne: Cell and Molecular Biology
• Status: Published
• Forskningsgrupp: Neurogastroenterology
• ISBN/ISSN/Övrigt: ISSN: 1573-9546