@article{medland_pohl_edwards_frandsen_bagley_li_moeser_2016, title={Early life adversity in piglets induces long-term upregulation of the enteric cholinergic nervous system and heightened, sex-specific secretomotor neuron responses}, volume={28}, ISSN={["1365-2982"]}, DOI={10.1111/nmo.12828}, abstractNote={AbstractBackgroundEarly life adversity (ELA) is a risk factor for the later‐life onset of gastrointestinal (GI) diseases such as irritable bowel syndrome (IBS); however, the mechanisms are poorly understood. Here, we utilized a porcine model of ELA, early weaning stress (EWS), to investigate the influence of ELA on the development and function of the enteric nervous system (ENS).MethodsFemale and castrated male (Male‐C) piglets were weaned from their sow either at 15 days of age (EWS) or 28 days of age (late weaning control, LWC). At 60 and 170 days of age, ileal mucosa‐submucosa preparations were mounted in Ussing chambers and veratridine‐ and corticotropin releasing factor (CRF)‐releasing factor‐evoked short circuit current (Isc) responses were recorded as indices of secretomotor neuron function. Enteric neuron numbers and the expression of select neurotransmitters and their receptors were also measured.Key ResultsCompared with LWC pigs, female, but not Male‐C EWS, pigs exhibited heightened veratridine‐induced Isc responses at 60 and 170 days of age that were inhibited with tetrodotoxin and atropine. Ileum from EWS pigs had higher numbers of enteric neurons that were choline acetyltransferase positive. Markers of increased cholinergic signaling (increased acetylcholinesterase) and downregulated mucosal muscarinic receptor 3 gene expression were also observed in EWS pigs.Conclusions & InferencesThis study demonstrated that EWS in pigs induces lasting and sex‐specific hypersensitivity of secretomotor neuron function and upregulation of the cholinergic ENS. These findings may represent a mechanistic link between ELA and lifelong susceptibility to GI diseases such as IBS.}, number={9}, journal={NEUROGASTROENTEROLOGY AND MOTILITY}, author={Medland, J. E. and Pohl, C. S. and Edwards, L. L. and Frandsen, S. and Bagley, K. and Li, Y. and Moeser, A. J.}, year={2016}, month={Sep}, pages={1317–1329} } @article{chang_frandsen_gadsby_2017, title={Prostaglandin synthesis by the porcine corpus luteum: effect of tumor necrosis factor-alpha}, volume={58}, ISSN={["1879-0054"]}, DOI={10.1016/j.domaniend.2016.07.001}, abstractNote={The porcine corpus luteum (CL) displays delayed sensitivity to PGF-2α (luteolytic sensitivity, [LS]) until days 12 to 13 of cycle. The control of LS is unknown, but it is temporally associated with macrophage (which secrete tumor necrosis factor-α; TNF-α) infiltration into the CL. Other studies showed that TNF-α induces LS in vitro and that prostaglandins (PGs) may be involved in this mechanism. In experiment 1, PGF-2α and PGE secretion by luteal cells (LCs) was measured on days 4 to 14 of the estrous cycle, and the expression of PTGFS/AKR1B1 and PTGES/mPGES-1, determined by Western blot, before (day 7) vs after (day 13) the onset of LS. Results showed that the PGF-2α:PGE ratio increased significantly (P < 0.05) from day 4 to 13-14, and PTGFS/AKR1B1 and PTGES/mPGES-1 were significantly increased (P < 0.05) on day 13 (vs day 7). In experiment 2, LCs were collected from porcine CL at early (∼days 4-6) or mid (∼days 7-12) stages of the estrous cycle and cultured with 0, 0.1, 1, or 10 ng/mL TNF-α. Results showed that TNF-α significantly increased (P < 0.05) messenger RNA (mRNA) expression of cyclooxygenase (COX)-2 and mPGES-1 but not AKR1B1. TNF-α had no significant effects on AKR1B1 or mPGES protein abundance. TNF-α significantly increased (P < 0.05) PGE-2 but had no effect on PGF-2α secretion or on the PGF-2α:PGE2 ratio. In conclusion, although TNF-α increased COX2 and mPGES-1 mRNA, and PGE-2 secretion in vitro, it did not increase the PGF-2α:PGE2 ratio. Studies are currently directed toward exploring other pathways (eg, FP receptor signaling) by which TNF-α induces LS in the porcine CL.}, journal={DOMESTIC ANIMAL ENDOCRINOLOGY}, author={Chang, J. and Frandsen, S. and Gadsby, J. E.}, year={2017}, month={Jan}, pages={53–62} }