Neurophysiopathology Group

Director:
Dr. Jorge Goldstein. Established Researcher (Associate, CONICET); Full-time teaching appointment

Personnel:
Lic. Carla Tironi-Farinati, Ph.D. Student and Research appointment

Colaborators:
Prof. Dr. César Fabián Loidl, Instituto de Biología Celular y Neurociencias "Prof. E. De Robertis", Fac. de Medicina, UBA-Conicet.
Prof. Dr. Juan José López-Costa, Instituto de Biología Celular y Neurociencias "Prof. E. De Robertis", Fac. de Medicina, UBA-Conicet.
Dr. Mariano Fernández Miyakawa, Instituto de Patobiología, INTA Castelar.
Dra. Patricia Geoghegan, Centro Nacional de Control de Calidad de Biológicos - ANLIS "Dr. Carlos G. Malbrán".
Dra. Elisa Cebral, Instituto de Fisiología, Biología Molecular y Neurociencias, Fac. de Ciencias Exactas y Naturales, UBA-Conicet.
Prof. Dr. Luis Barbeito, Instituto Pasteur de Montevideo, Uruguay.

Former lab members:
Javier Boccoli: performed graduate tesis.

Contact:
Laboratrio de Neurofisiopatología
Departamento de Fisiología
Facultad de Medicina - Universidad de Buenos Aires
Paraguay 2155 piso 6 (Sector Uriburu)
CABA (C1121ABG) Argentina
Télefono: ++ 54 11 5 950 9500 int. 2135
E-mail: jogol@fmed.uba.ar

Our aim

Shiga toxin (Stx) from Enterohemorrhagic Escherichia coli (STEC) is the main cause of hemorrhagic colitis, Hemolytic Uremic Syndrome (HUS) and acute encephalopathy in humans, being Argentina the first country with 400 new cases of HUS per year. CNS dysfunction caused by STEC is one of the most risk factors among infant mortality at the acute period of illness. The aim of our lab is to study the physiopathology of Stx2 in the Central Nervous System (CNS), because a high incidence from fatal outbreaks of intoxication by STEC originated from neurological symptoms. However the direct Stx effect in CNS neurons has not yet been established. Therefore we propose to develop a neurotoxic animal model of intracerebroventricular Stx2 administration, and compare it with a systemic one in rats. Neuroglial and microvasculature brain alterations are studied by specific neuronal, glial and cell injury markers, and by changes in neurotransmitter expression. Molecules capable to neutralize Stx2 neurotoxic effect will be administered. The preceding studies are analyzed by light, fluorescent, and electron microscopies, and by molecular strategies, and will contribute to understand key pathogenic events triggered by Stx2 during CNS intoxication.

Recent publications:

Intracerebroventricular Shiga toxin 2 increases the expression of its receptor globotriaosylceramide and causes dendritic abnormalities. Tironi-Farinati C, Loidl CF, Boccoli J, Parma Y, Fernandez-Miyakawa ME, Goldstein J. Journal of Neuroimmunology 222: 48-61, 2010.

Clostridium perfringens epsilon toxin increases the small intestinal permeability in mice and rats. Goldstein J, Morris WE, Loidl CF, Tironi-Farinatti C, McClane BA, Uzal FA, Fernandez Miyakawa ME. PLoS One. 2009 Sep 18;4(9):e7065.

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 J, Loidl C.F., Lopez-Costa J.J., Pistone Creydt V., Ibarra C., Goldstein J. Brain Research 1230:320-333, 2008.

Síndrome Urémico Hemolítico inducido por Escherichia coli enterohemorrágica. Ibarra C, Goldstein J, Silberstein C, Zotta E, Belardo M, Repetto HA: Arch Argent Pediatr 106: 435-442, 2008.

Intracerebroventricular administration of Shiga toxin type 2 induces striatal neuronal death and glial alterations: an ultrastructural study. Goldstein J, Loidl CF, Pistone Creydt V, Boccoli J, Ibarra C. Brain Research 1161:106-15, 2007.

PreproThyrotropin-Releasing Hormone178-199 (preproTRH178-199) Affects Tyrosine Hydroxylase Biosynthesis in Hypothalamic Neurons: a Possible Role for Pituitary Prolactin Regulation. J. Goldstein, M. Perello, E.A. Nillni. Journal of Molecular Neuroscience 31 (1): 1-14, 2007.

Role of the Shiga toxin in the hemolytic uremic syndrome. Pistone Creydt V, Nuñez P, Boccoli J, Silberstein C, Zotta E, Goldstein J, Ibarra C. Medicina 66 (Supl III): 11-15, 2006.

Regulation of Hypothalamic Prohormone Convertases 1 and 2 and effects on processing of prothyrotropin releasing hormone. Sanchez VC, Goldstein J, Stuart R, Hovanesian V, Huo L, Munzberg H, Friedman TC, Liu Y, Bjorbaek C, Nillni EA. Journal of Clinical Investigation, 114 (3): 357-369, 2004.