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Efectos de la Tibolona sobre la neuroinflamación Andrea Crespo Castrillo Laboratorio de Esteroides Neuroactivos Instituto Cajal, CSIC La Tibolona es un esteroide sintético usado para la prevención de la osteoporosis y el tratamiento de los síntomas relacionados con la menopausia en mujeres. Las acciones de las Tibolona se deben en su mayoría a la actividad estrogénica, aunque también se han descrito efectos androgénicos y progestágenos según el tejido en el que actúe. En estudios previos se ha visto que el estradiol es capaz de reducir la gliosis reactiva, por lo que nuestra hipótesis es que la Tibolona también es capaz de regular la gliosis y por lo tanto la neuroinflamación. Para ello hemos usado diferentes modelos de inflamación, tanto in vitro como in vivo. In vitro hemos utilizado cultivos primarios de microglía a los que administrábamos ácido palmítico para producir la inflamación y después aplicábamos Tibolona para ver el efecto sobre esta inflamación. Hemos visto que la Tibolona es capaz de reducir tanto la muerte como la inflamación en nuestro modelo. In vivo hemos usado el modelo de lesión penetrante y administramos distintas dosis de Tibolona para ver también su efecto en la inflamación. De momento hemos visto que el fármaco es capaz de reducir la astrogliosis. Effects of palmitic acid on autophagy in neurons and astrocytes Ana Ortiz Rodríguez Laboratorio de Esteroides Neuroactivos Instituto Cajal, CSIC After traumatic/hypoxic brain injury or during chronic obesity, fatty acids increase in brain parenchyma and trigger cell dysfunction and death. However, the underlying pathological mechanisms have not been established in nerve cells yet. Correlations between the consumption of high fat diets and cognitive impairment have been suggested and sex differences have been reported. Aims: The aim of this study was to assess the effect of palmitic acid, one of the most abundant saturated fatty acids in high fat diets, on cultured hippocampal neurons and cortical astrocytes. Methods: Neurons were obtained separately from male and female E17 mouse embryos and treated with palmitic acid or vehicle at 3 days in vitro (DIV). Neuronal death levels and different morphological parameters were analyzed at 4 DIV. Autophagic flux was determined after 4.5 hours of treatment with palmitic acid. Astrocytes were cultured from postnatal day 0-2 male or female mice pups, separately. Cell viability, nitrite production and autophagic flux in astrocytes were determined after 24 hours of treatment with palmitic acid. Results: A dose response curve showed that palmitic acid at a concentration of 100 μM induced death in male but not female neurons at 4 DIV. Neuronal morphology was not modified by lower concentrations of palmitic acid (50 μM) neither in male nor in female cultures. Furthermore, autophagic flux showed a tendency to decrease by palmitic acid (500 μM) in neurons. In astrocytes, palmitic acid (250-500 μM) reduced cell survival and autophagic flux beside an increased nitrite production. Conclusions: These results suggest that palmitic acid increases cell death and decreases autophagic flux in cultured neurons and astrocytes. In addition, male hippocampal neurons are more sensitive to palmitic acid lipotoxicity than female hippocampal neurons.
