Intracerebroventricular administration of Shiga toxin type 2 altered the expression levels of neuronal nitric oxide synthase and glial fibrillary acidic protein in rat brains.

BOCCOLI JAVIER; LOIDL FABIAN; LOPEZ-COSTA JUAN JOSÉ; PISTONE CREYDT VIRGINIA; IBARRA CRISTINA; GOLDSTEIN JORGE

BRAIN RESEARCH

ELSEVIER SCIENCE BV

Año: 2008 vol. 1230 p. 320 - 333

0006-8993

Shiga toxin (Stx) from enterohemorrhagic Escherichia coli (STEC) is the main cause ofhemorrhagic colitis which may derive into Hemolytic Uremic Syndrome (HUS) and acuteencephalopathy, one of the major risk factors for infant death caused by the toxin. We havepreviously demonstrated that intracerebroventricular administration of Stx2 causesneuronal death and glial cell damage in rat brains. In the present work, we observed thatthe intracerebroventricular administration of Stx2 increased the expression of glial fibrillaryacidic protein (GFAP) leading to astrogliosis. Confocal microscopy showed reactiveastrocytes in contact with Stx2-containing neurons. Immunocolocalization of increasedGFAP and Stx2 in astrocytes was also observed. This insult in the brain was correlated withchanges in the expression and activity of neuronal nitric oxide synthase (nNOS) by using theNADPH-diaphorase histochemical technique (NADPH-d HT). A significant decrease in NOS/NADPH-d-positive neurons and NOS/NADPH-d activity was observed in cerebral cortex andstriatum, whereas an opposite effect was found in the hypothalamic paraventricularnucleus. We concluded that the i.c.v. administration of Stx2 promotes a typical pattern ofbrain injury showing reactive astrocytes and an alteration in the number and activity ofnNOS/NADPH-d. According to the functional state of nNOS/NADPH-d and to brain cellmorphology data, it could be inferred that the i.c.v. administration of Stx2 leads to either aneurodegenerative or a neuroprotective mechanism in the affected brain areas. The presentanimal model resembles the encephalopathy developed in Hemolytic Uremic Syndrome(HUS) patients by STEC intoxication.©