SHIGA TOXIN 2 CHANGES NEUROTRANSMITTER EXPRESSION OF NEURONS FROM MURINE MOTOR CORTEX AND STRIATUM

LUCAS ELIZAGARAY; ADRIANA CANGELOSI; ALIPIO PINTO; DAVID ARENAS; JORGE GOLDSTEIN; CLARA BERDASCO; PATRICIA GEOGHEGAN

Mendoza

Congreso; XXXVI REUNION CIENTIFICA ANUAL DE LA SOCIEDAD DE BIOLOGIA DE CUYO; 2018

SOCIEDAD DE BIOLOGIA DE CUYO

Shiga toxin 2 (Stx2) from enterohemorrhagic Escherichia coli (EHEC) causes hemolytic uremic syndrome (HUS) and acuteencephalopathy, which may lead to fatal outcomes in patients. Neurological signs of this disorder include decerebrate posturing,hemiparesis, ataxia, seizures and changes in the level of consciousness (from lethargy to coma). When neurological symptoms areevidenced mortality rate may rise up to 40%, significantly higher in comparison to that produced by HUS (5%). The motor areas of thebrain are frequently affected in patients infected with EHEC. The aim of this study was to determine whether Stx2 changes theexpression of neurotransmitters and/or the number of dopaminergic, GABAergic and glutamatergic neurons from the motor cortex andstriatum. NIH Swiss male mice (n=4) were treated intravenously with vehicle (control) or 1ηg of Stx2 (100μl per mouse). All animalswere intracardially fixed on the 4th day (day of the injection considered as day 0) and their brains were subjected to immunofluorescencewith an anti-tyrosine hydroxylase (TH) antibody to identify dopaminergic axons from substance nigra, anti-GABA and anti-glutamateantibodies to identify motor cortex GABAergic and glutamatergic neurons. Stx2 increased the striatal expression of TH in comparison tocontrol-treated mice (36.17±5.44 vehicle vs 98.89±2.52 Stx2; in IOD; p<0.05). On the other hand, Stx2 reduced the expressions ofGABA (2.1±0.24 vehicle vs 1.38±0.09 Stx2; in IOD; p<0.05) and glutamate (1.82±0.13 vehicle vs 0.9±0.03 Stx2; in IOD; p<0.05) perneuron in motor cortex, while no significant changes were found in the number of GABAergic and glutamatergic positive neuronsbetween control and Stx2 groups. These results may suggest a compensatory mechanism carried out by substancia nigra ́s nigrostriatalneurons. The presented results together with previous published ones may indicate that the increased expression of TH compensates alack of striatal neurons from the extra pyramidal system that suffered from a neurodegenerative process. In addition, the decreased onGABA and glutamate expression in the murine motor cortex could be a consequence of a reduction on neuronal metabolism produced byribotoxic stress from Stx2 action. We concluded that Stx2 changed the expression of the 3 main neurotransmitters that are responsible forthe pyramidal and extra-pyramidal signalling pathways involved with the reported motor alterations in patients and animal models.