SHIGA TOXIN 2 (STX2) FROM ENTEROHEMORRHAGIC Escherichia coli (EHEC) PRODUCED ANOREXIA THROUGH REDUCED GHRELIN EXPRESSION AND DAMAGE IN HYPOTHALAMIC ARCUATE (ARC) AND PARAVENTRICULAR (PVN) NUCLEI

CANGELOSI ADRIANA; GOLDSTEIN JORGE; PINTO ALIPIO; PERELLO MARIO; BRENER GABRIELA JESICA ; GEOGHEGAN PATRICIA

CABA

Simposio; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Anorexia and weight loss are observed in patients by Stx2 intoxication from EHEC which may leadto coma and death. Loss of appetite may be due to a neurotoxic effect of Stx2 on hypothalamic orexigenic neurons or failure of orexigenic signals from the gut. Ghrelin is an orexigenic hormone produced by enteroendocrine cells that acts through its hypothalamic Arc and/or PVN neuronal receptors. The aim of this study was to determine whether Stx2: i) induces loss of weight, ii) changes the expression of ghrelin in the gut, and iii) affects the parenchyma of Arc and PVN. NIH mice (n=4) were treated intravenously with vehicle (100µl of saline solution) or Stx2 (1ηg/mice). Animal body weight and food intake were monitored daily for 4 days. Another control group (pair fed) was included to determine whether the loss of weight was only caused by an anorexigenic effect or by a metabolic component. The amount of food provided to this group was the exact amount of food eaten by the Stx2 treated mice. Then, the animals were fixed and their stomachs and brains were subjected to immunofluorescence with anti-Ghrelin, anti-GFAP and anti-NeuN. After 4 days, the Stx2 treated mice significantly lost weight, as compared to the vehicle ones (3.05±0.58g control and -1.01±0.32g Stx2). Weight loss was accompanied by a significant decrease of food intake (5.04±0.46g control and 3.10±0.28g Stx2) and in the number of ghrelin immunopositive cells in the stomach (13.97±0.68 cells control and 7.73±0.95 cells Stx2). GFAP expression (30.43±1.73 AU control and 44.65±1.40 AU Stx2, in IOD) and the number of immunopositive NeuN abnormal neurons(0 cells control and 3.18±1.83 cells Stx2) were increased in the ARC and PVN Of Stx2 treated mice (p