Research projects

Such as brain glucose hypometabolism (BGH), oxidative stress, neuroinflammation and insulin resistance (RI) are pathogenic alterarions present  in several neurodegnerative diseases with distinct aethiologies. Accordingly we propose to investigate the possible metabolic alterations in the lateral amyotrophic sclerosis of the TDP43 mice as an experimental model of this disease. Previously we had  reported a BGH and RI in mice with tauothopathy, findings of great interest to investigate the effects of several drugs on these alterations. Related with the TDP-43 mice we found a tendency to increase brain glucose metabolism as compared with the wild type (WT) animals, that in females was statistically significant in the brain stem and cerebellum. Related with the genic expresión we found differences between male and female TDP-43 mice. In fact  in the hippocampus of female mice we observed an increase of the Slc2a3 and Mtor genes expresion with a negative feedback for the Gsk3 and Pik3r1 genes, while no changes were detected for Akt and Irs1 ones. These findings are probably related with an increase of the anaerobic glycolysis, which is also present in the Parkinson, Alzheimer and Huntington diseases. In mice with tauothopathy an insulin resistance was found, which improves after metformin treatment. Also, in TDP-43 mice the resistance to insulin was  determined after the i.p. glucose overload and according with the HOMA procedure. In the case that alterations can  be found, the mice will be treated with metformin, exenatide or literaglutide. Finally a signicant part of our work at the end of this scientific project has been dedicated in writting and processing the publication of several papers.