Characterizing cortical bioenergetics in a mouse model of Alzheimer’s disease

Abstract

Alzheimer's Disease (AD) currently represents the most common neurodegenerative disease worldwide. The complete underlying mechanisms of its physiopathology are still unknown, but brain bioenergetics and the endocannabinoid system (ECS) have emerged as potential novel therapeutic targets in AD. This project aimed to clarify whether mitochondrial alterations could be linked with the behavioural alterations found in a mouse model of AD treated with cannabinoid drugs, considering sex differences as an important factor. First, we assessed the expression of the oxidative phosphorylation system (OXPHOS) complexes by Western Blot assays in cortex samples from 12-month-old WT and APP/PS1 male and female mice. Despite no significant results were obtained, behavioural correlations indicate an association between conduct and molecular processes. Furthermore, we performed liquid chromatography-mass spectrometry to quantify the most relevant metabolites of the Krebs cycle. Our results suggest a few alterations in APP/PS1 male mice in some metabolites and enzymes that could have a role in AD’s pathology. Overall, this study opens the possibility of a feasible interesting link between bioenergetics, cannabinoids and AD pathology. Even though, further research should be performed to achieve a better knowledge of the disease and explore these new targets to improve early diagnosis and therapeutic approaches.