Defective tumor necrosis factor-alpha-dependent control of astrocyte glutamate release in a transgenic mouse model of Alzheimer disease.

The cytokine tumor necrosis factor-alpha (TNFalpha) induces Ca2+-dependent glutamate release from astrocytes via the downstream action of prostaglandin (PG) E2. By this process, astrocytes may participate in intercellular communication and neuromodulation. Acute inflammation in vitro, induced by adding reactive microglia to astrocyte cultures, enhances TNFalpha production and amplifies glutamate release, switching the pathway into a neurodamaging cascade (Bezzi, P., Domercq, M., Brambilla, L., Galli, R., Schols, D., De Clercq, E., Vescovi, A., Bagetta, G., Kollias, G., Meldolesi, J., and Volterra, A. (2001) Nat. Neurosci. 4, 702-710). Because glial inflammation is a component of Alzheimer disease (AD) and TNFalpha is overexpressed in AD brains, we investigated possible alterations of the cytokine-dependent pathway in PDAPP mice, a transgenic model of AD. Glutamate release was measured in acute hippocampal and cerebellar slices from mice at early (4-month-old) and late (12-month-old) disease stages in comparison with age-matched controls. Surprisingly, TNFalpha-evoked glutamate release, normal in 4-month-old PDAPP mice, was dramatically reduced in the hippocampus of 12-month-old animals. This defect correlated with the presence of numerous beta-amyloid deposits and hypertrophic astrocytes. In contrast, release was normal in cerebellum, a region devoid of beta-amyloid deposition and astrocytosis. The Ca2+-dependent process by which TNFalpha evokes glutamate release in acute slices is distinct from synaptic release and displays properties identical to those observed in cultured astrocytes, notably PG dependence. However, prostaglandin E2 induced normal glutamate release responses in 12-month-old PDAPP mice, suggesting that the pathology-associated defect involves the TNFalpha-dependent control of secretion rather than the secretory process itself. Reduced expression of DENN/MADD, a mediator of TNFalpha-PG coupling, might account for the defect. Alteration of this neuromodulatory astrocytic pathway is described here for the first time in relation to Alzheimer disease.

Ideario social-educativo en D. Rafael María de Labra.

Estudiar la educación española de finales del XIX y concretamente la figura de Rafael María de Labra. Se realiza una investigación sobre D. Rafael M. de Labra en sus múltiples facetas como jurista, político publicista y hombre preocupado de la educación nacional. Se expone su prolífera actividad en la sociedades económicas, Ateneo de Madrid, Sociedad Abolicionista Española, Institución Libre de Enseñanza, entre otras. Aparece como un hombre liberal radical y vinculado al espíritu democrático krausista e institucionalista. Trabaja en pro de una reforma social y es uno de los principales promotores de las compañías organizadas por la institución en pro de una reforma de la educación nacional. Para ello se divide el trabajo en una primera parte donde se analiza la situación político-social y cultural de España en la segunda mitad del XIX; después otro apartado con la vida y obra de Labra; el tercero se ocupa de su pensamiento político; y en el último se desarrolla el pensamiento de Labra ante la política educativ. Investigación documental. Labra considera que el problema político y social no es legislativo sino de política educativa, por ello la reforma de la enseñanza primaria pública es vital, sin ella no habrá vida política, social ni moral. Promulga la libertad absoluta de enseñanza, de cátedra y profesional. Defiende una enseñanza primaria laica, obligatoria y gratuita, que dependa, de manera transitoria del Estado al que le reconoce una acción en calidad de tutor. La educación secundaria necesita una reforma urgente por ser exclusiva de ciertas clases sociales, y será la iniciativa particular quien cubra esa enseñanza. También debe reformarse la universidad que se ocupará exclusivamente de estudios científicos a los que el Estado debe apoyar, dejando las carreras profesionales a cargo de particulares. Se puede considerar a Labra como pionero de nuevos caminos y orientaciones que obligan a la opinión y poderes públicos, a concienciarse de la importancia de la educación popular, de la educación de la mujer, de las enseñanzas técnicas y científicas, provocando cambios de ideas y reformas de la enseñanza nacional.

Intrauterine food restriction alters the expression of uncoupling proteins in brown adipose tissue of rat newborns

A previous study from our laboratory showed that maternal food restriction (MFR) delays thermoregulation in newborn rats. In neonates brown adipose tissue (BAT) is essential for thermogenesis due to the presence of uncoupling proteins (UCPs). The aim of this study was to evaluate the influence of MFR on the UCPs mRNA and protein expression in BAT and skeletal muscle (SM) of the newborn rat. Female Wistar EPM-1 control rats (CON) received chow ad libitum during pregnancy, whereas food-restricted dams (RES) received 50% of the amount ingested by CON. Fifteen hours after birth, the litters were weighed and sacrificed. Blood was collected for hormonal analysis. BAT and SM were used for determination of UCPs mRNA and protein expression, and Ca2+-ATPase sarcoplasmic reticulum (SERCA1). RES pups showed a significant reduction in body weight and fat content at birth. MFR caused a significant increase in the expression of UCP1 and UCP2 in BAT, without changes in UCP3 and SERCA1 expression in BAT and SM. No differences between groups were found for leptin, T4 and glucose levels. RES pups showed increased insulin and decreased T3 levels. The delay in development of thermoregulation previously described in RES animals appears not to result from impairment in thermogenesis, but from an increase in heat loss, since MFR caused low birth weight in pups, leading to greater surface/volume ratio. The higher expression of UCP1 and UCP2 in BAT suggests a compensatory mechanism to increased thermogenesis. (C) 2011 Elsevier Ltd. All rights reserved.