Amyloid-beta oligomers (AβO) have been proposed as the most potent neurotoxic and inflammation inducers in Alzheimer’s disease (AD). AβO contribute to AD pathogenesis by impairing the production of several cytokines and inflammation-related signaling pathways, such as the Janus kinases/signal transducer of transcription factor-3 (JAK/STAT3) pathway. STAT3 modulates glial activation, indirectly regulates Aβ deposition, and induces cognitive decline in AD transgenic models. However, in vivo studies using an AβO microinjection rat model have not yet explored STAT3 role. The main purpose of this study was to elucidate if a single microinjection of AβO could promote an increased expression of STAT3 in glial cells favoring neuroinflammation and neurodegeneration. We designed a model of intrahippocampal microinjection and assessed glial activation, cytokines production, STAT3 expression, and neurodegeneration in time. Our results showed robust expression of STAT3 in glial cells (mainly in astrocytes) and neurons, correlating with neuronal death in response to AβO administration. A STAT3 inhibition assay conducted in rat primary hippocampal cultures, suggested that the induction of the transcription factor by AβO in astrocytes leads them to an activation state that may favor neuronal death. Notwithstanding, pharmacological inhibition of the JAK2/STAT3 pathway should be focused on astrocytes because it is also essential in neurons survival. Overall, these findings strongly suggest the participation of STAT3 in the development of neurodegeneration.
La presente investigación ofrece un estudio novedoso acerca de la capacitación en las pequeñas y medianas empresas de la industria manufacturera en México, el objetivo principal fue identificar el comportamiento de los sueldos y las ventas en función a la inversión en capacitación. El método consistió en el análisis multivariable con cuadrados mínimos ordinarios, efectos fijos, y con series de tiempo de la información recabada por el INEGI en la encuesta anual de la industria manufacturera durante ocho años. Los resultados revelan un incremento significativo en los sueldos y en las ventas en aquellas empresas que reportaron invertir en capacitación, siendo el hallazgo principal la identificación de óptimos de inversión en capacitación. La originalidad del artículo es identificar el monto de la inversión anual en capacitación para maximizar las ventas y los sueldos por persona. Una limitación radica en la dificultad de obtener intervalos de estimación.
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