Age-dependent differences in galanin-dependent colonic fluid secretion after infection with Salmonella typhimurium

Abstract

Epithelial cells lining the colon do not normally express galanin type 1 receptors (Gal1Rs). However, subsequent to infection with enteric pathogens such as Salmonella typhimurium, the Gal1R is rapidly upregulated in colonocytes where it contributes to the excess fluid production associated with diarrhoea. Humans infected with non-typhoid Salmonella respond differently according to age: infants develop diarrhoea but not bacteraemia and survive, while the elderly become bacteraemic and die. Thus the aim of this study was to determine if age-related differences exist in response to S typhimurium infection in mice, and whether these differences are due to altered Gal1R expression. Wild-type C57BL/6J mice that were 2 and 15 months old, as well as 2-month-old Gal1R knockout mice, were infected by gavage. Young wild-type mice expressed Gal1R in response to infection, had increased colonic fluid secretion, low rates of bacteraemia and survived. In contrast, 15-month-old wild-type mice expressed fewer Gal1Rs in response to infection, had attenuated increases in colonic fluid secretion, high rates of bacteraemia and died. A similar profile was noted in 2-month-old Gal1R knockout mice. Addition of polyethylene glycol to the drinking water of 15-month-old wild-type mice increased colonic fluid secretion and reduced rates of bacteraemia to those observed in 2-month-old wild-type mice and eliminated fatalities. The difference in response to S typhimurium infection with age may be due, at least in part, to decreased Gal1R expression and decreased amounts of colonic fluid secretion.

Galaninergic intramural nerve and tissue reaction to antral ulcerations

“…The decrease in galanin expression observed in the colon samples could partially result from the fact that intestinal tissues were heavily damaged by the severe pathological process and some structures expressing galanin and its receptors were destroyed. In rodents, experimentally induced colitis resulted in an increase in the galanin expression in the gastrointestinal nerve structures: in mice after infection with pathogenic bacteria, and in rats in trinitrobenzene sulphonic acid induced colitis . The changes in galanin expression observed in the latter study were dependent upon the exact time point of colitis and the extent of tissue damage.…”

Prolonged Acetylsalicylic-Acid-Supplementation-Induced Gastritis Affects the Chemical Coding of the Stomach Innervating Vagal Efferent Neurons in the Porcine Dorsal Motor Vagal Nucleus (DMX)

“…Similar upregulation of GAL synthesis has been observed in enteric neurons following formalin-induced porcine colitis (Gonkowski et al 2010). Inflammatory GAL induction in murine colitis is accompanied by parallel augmentation of GAL1 receptor expression in colonic epithelium (Marrero et al 2000; Matkowskyj et al 2009), thus constituting a subsequent link of the GAL signaling pathway. To date, there has been no data specifying the final functional destination of the GAL, although it may affect the secreting neuron itself, postganglionic secondary neuron, or may act on other cells of an inflammatory focus.…”

Physiology, Signaling, and Pharmacology of Galanin Peptides and Receptors: Three Decades of Emerging Diversity

“…In vivo, galanin gene expression and peptide secretion in the nervous system are modulated by chronic stress (Holmes et al, 1995;Sweerts et al, 1999;Sergeyev et al, 2005;Sciolino et al, 2012), axotomy Burazin and Gundlach, 1998) (Matkowskyj et al, 2000)/C57BL/6J Decreased fluid secretion in the GI tract after infection with enteric pathogens (Matkowskyj et al, 2000) No different from WT in response to Salmonella typhimurium infection (Matkowskyj et al, 2009) Decreased diarrhea after infection with rhesus rotavirus (Hempson et al, 2010a) GAL 1 /Deltagen (San Carlos, CA)/129P2/OlaHsd  C57BL/6 GAL 2 /Lexicon Genetics (The Woodlands, TX)/129/SvEvBrd  C57BL/6…”