CONICET | Buscador de Institutos y Recursos Humanos

Type 2 diabetes (DBT2) is a metabolic disorder clinically characterized by an increase in blood glucose levels. It is well known that DBT2 causes neurodegeneration, however, molecular mechanisms involved in this process are not clear yet. Several hypotheses were proposed in order to elucidate molecular changes and cascades involved in neurodegeneration caused by DBT2. Amongst them, the ones related to RAGE products, stress signaling and chronic inflammation are the best investigated. Furthermore, high glucose levels were also proposed as a mechanism for neurodegeneration. Pre-diabetes 2 (preDBT) is considered to be a step before DBT2, with glucose levels intermediate between normal and DBT levels. PreDBT is thought to be reversible. However, it is not well understood if pre-DBT syndrome per se, or the progression to DBT2, could cause neurodegeneration or synaptic plasticity impairment. In order to find out which mechanisms are involved in these processes, and to identify whether they start during pre-DBT, we decided to investigate if neurodegeneration could take place in these early stages. For this reason, we incubated primary mixed cultures (astrocytes and neurons) with sera from patients with altered fasting glucose (AG) for seven days. As controls we used sera from persons with normal fasting glucose values (NG). Sera from both groups differed only in glucose values, and had normal values for insulin, cholesterol and triglycerides. Our results indicate that sera from AG patients induced changes in astrocytes number and shape. These cultures also showed altered neuron morphology, together with a decrease in the number of neurons counted. Both the increase in astrocyte and the reduction in neurons percentage correlate with glucose levels. These preliminary results would lead us to hypothesize that the increase in glucose values could start changes in neurons and glia that are compatible with neurodegeneration.