Sera from prediabetic patients induce changes in neurons and glia in mix primary cultures

MARIA PILAR CANAL; ANNA DE TOMAS LIORO; CECILIA PUGLIESE; ADELINA BADOLATI; MARIA VERONICA BAEZ

Mar del Plata

Congreso; Reunion conjunta SAIC SAI SAFIS; 2018

SAIC, SAI, SAFIS

Type 2 diabetes (DBT2) is a metabolic disorder clinically characterizedby an increase in blood glucose levels. It is well known thatDBT2 causes neurodegeneration, however, molecular mechanismsinvolved in this process are not clear yet. Several hypotheses wereproposed in order to elucidate molecular changes and cascadesinvolved in neurodegeneration caused by DBT2. Amongst them,the ones related to RAGE products, stress signaling and chronicinflammation are the best investigated. Furthermore, high glucoselevels 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 understoodif pre-DBT syndrome per se, or the progression to DBT2,could cause neurodegeneration or synaptic plasticity impairment. Inorder to find out which mechanisms are involved in these processes,and to identify whether they start during pre-DBT, we decided to investigateif neurodegeneration could take place in these early stages.For this reason, we incubated primary mixed cultures (astrocytesand neurons) with sera from patients with altered fasting glucose(AG) for seven days. As controls we used sera from persons withnormal fasting glucose values (NG). Sera from both groups differedonly in glucose values, and had normal values for insulin, cholesteroland triglycerides. Our results indicate that sera from AG patientsinduced changes in astrocytes number and shape. These culturesalso showed altered neuron morphology, together with a decreasein the number of neurons counted. Both the increase in astrocyteand the reduction in neurons percentage correlate with glucose levels.These preliminary results would lead us to hypothesize that theincrease in glucose values could start changes in neurons and gliathat are compatible with neurodegeneration.