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Significance of brain glucose hypometabolism and of altered insulin signal transduction in an experimental model of amiotrophic lateral esclerosis (ALE)

19th national competition for scientific and technical research

Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS): Molecular Etiology and Novel Treatments

Senior Researcher : Enrique Blázquez Fernández

Research Centre or Institution : Universidad Complutense de Madrid

Abstract

Many neurodegenerative diseases show common pathogenic alterations but with distinct ethiologies. They are brain glucose hypmetabolism (BGHM), oxidative stress, neuroinflammation and resistance to insulin action. Accordingly we propose to study the possible metabolic changes to in the lateral amyotrophic sclerosis (LAS) with the use of the TDP-43 mice, an experimental model of this disease. Previously we have reported a BGHM and insulin resistance in mice with tauthopathy (TAU)  which is of great interest to investigate the effects of  different drugs on these alterations. Thus, in TAU mice treated  chronically with metformin the insulin resistance decreases while the brain glucose metabolism( BGM) was improved. Related with the LAS mice (TDP-43) we did not find significant differences of the BGM between males TDP-43 and their controls (WT). However in the females TDP-43 a significant increase of BGM in the troncoencephalic and cerebellum was found. Nevertheless when we compare the data from TDP-43 males and females  we did not observed difference statistically significant. Furthermore  the study of the brain genic expresión and of the content of insulin receptors and their transducers in the brain of WT and TDP-43 are already done, while the data obtained on the brain protein content  (Western blot) of the cerebral cortex and hippocampus are under the processing procedure. In addition the study of the expresson of the brain genes related with the glucose metabolism in hippocampus are already ended. In fact we have found in TDP-43 females a significant increase in the genic expresión of GLUT-3 and mTORC-1 and a significant decrease of PI3K y GSK3, but in TDP-43 males these effects were not so relevant. These findings confirm at a biochemical level a greater brain metabolic activity in the TDP-43 females than in the males, which open new expectancy in the pathogenia of this disease. Also the studies that still we have to done may augment the value of these observations. 

 

Scientific Production
 
Magazine Articles 4
Communications at national conferences 3
Communications at international conferences -

 

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