Role of astrocytes in age-associated cognitive loss: molecular, behavioural and clinical aspects.
The IIBB-CSIC group is focused in the mechanisms underlying the age-related cognitive loss and testing preventive strategies of healthy aging. This research is based in the use of mouse models of senescence (SAMP8) and Alzheimer’s disease (3xTg-AD and 5XFAD). Mechanisms are further analyzed with the use of neuron and astrocyte cultures and human brain tissue. The group has recently demonstrated that physical exercise protects from cognitive loss in Tg AD mouse models through an improvement of brain tissue redox homeostasis and activation of neurotrophic and survival pathways, such as SIRT1, GDNF and BDNF. Also, it was highlighted the importance of astrocytes in neurorescue therapies. Mechanisms of the beneficial effects of resveratrol and melatonin through these pathways are under study.
Collaborations ongoing within the Consolider consortium include the characterization of changes in cognitive and general behavior and Alzheimer’s disease histological markers in newly engineered mice by the group of Angel Nebreda (IRB). Effects of two different anti-aging treatments on SAMP8 mouse brain and behavior are under study in collaboration with the groups of Enrique de la Rosa (CBM) and Dolores Ledesma (CBMSO), respectively. Mouse embryo fibroblasts were engineered to study a PS1 mutation recently described by the group of José Luis Molinuevo (Hospital Clínic, IDIBAPS). A study of lymphocytes immortalized from Alzheimer’s disease patients (provided by A. Martín-Requero, CBM) has been recently undertaken to collaborate in the search for peripheral disease markers of Alzheimer’s disease with the group of José Luis Molinuevo.
Characterization of 5XFAD mice by immunohistochemistry and positron emission tomography, showing advanced amyloid deposition and its detection with the radiotracer [18F]-Florbetapir. For details see full paper in http://www.sciencedirect.com/science/article/pii/S0197458012006604