Padronização de um método alternativo para diferenciação de células de neuroblastoma utilizando matriz extracelular rica em laminina para avaliação de ADAM10 e IDE em meios de cultivo hiperglicêmico e normoglicêmico

Abstract

Alzheimer’s disease (AD) is a gradual and progressive neurodegenerative disease characterized by cortical atrophy predominantly in the medial temporal lobe and, microscopically, by extensive neuronal losses and deposits called neurofibrillary tangles and senile plaques. Since the results of the Rotterdam study in 1992, it has been known that type 2 diabetes mellitus (T2DM) increases the risk of dementia. Patients with T2DM present structural brain changes and cognitive impairment, with a high risk of developing AD. These data suggest that insulin may play a fundamental role in brain activity and memory formation. Based on these findings, AD has been called “type 3 diabetes” (T3DM) or “cerebral diabetes” by some researchers. Some research groups have shown that ADAM10, the α-secretase that inhibits the formation of senile plaques and, therefore, is protective against AD, is altered in the blood of older adults with this dementia compared to cognitively healthy older adults. In this sense, the objective of this study was to verify whether there are differences in the levels and activity of ADAM10 in neuroblastoma cells (SH-SY5Y), differentiated and undifferentiated, cultured in regular and hyperglycemic cellular media, in a condition that simulates T2DM, as well as concomitant changes in the levels of proteins involved in the insulin pathway, particularly the insulin-degrading enzyme (IDE). The results showed that the extracellular matrix (ECM) maintains the differentiation of neuronal cells for a more extended period, even in an environment with a high glucose content. Furthermore, it was also possible to observe a reduction in ADAM10 and IDE levels in SH-SY5Y cells differentiated and cultured in a hyperglycemic environment. The results of this study highlight the importance of the ECM in maintaining neuronal differentiation in vitro. Furthermore, these results contribute to a deeper understanding of the molecular interactions between T2DM and AD and provide valuable suggestions for future research in these areas. The impact of this study is related to a better understanding of the biology of these diseases, highlighting the need for more studies related to the implementation of new clinical approaches to the treatment of AD, also observing the metabolic status of patients.