Effect of aging-dependent changes in lipid composition on membrane properties in hippocampal neurons

MAURICIO GERARDO MARTÍN; SEBASTIAN MUNCK; SILVIA A MENCHÓN; CARLOS G DOTTI

Jornada; Vlaams Instituut voor Biotechnologie (VIB) retreat.; 2009

Binding of the neurotrophin BDNF to the TrkB receptor is a major survival mechanism during embryonic development. In the aged brain however, BDNF levels are low, suggesting that additional mechanisms must have developed to activate TrkB and the downstream pro-survival molecules. We show that age-associated increase in TrkB activity is correlated with a mild yet progressive loss of cholesterol. This, in turn, is correlated with increased expression of the cholesterol catabolic enzyme cholesterol 24-hydroxylase. However, experiments using photoactivatable GFP inked to a farnesyl tail and single molecule tracking of AMPA receptors indicated that cholesterol loss during aging is also accompanied by plasma membrane changes that would result in reduced neuronal performance.