Your results confirm that a loss in synaptic MARCKS during aging is responsible for the impairment of certain aspects of neuronal function. Can you explain?
Laura: Our data suggest that part of the cognitive loss that accompanies aging is a consequence of a reduced association to the plasma membrane of the cholesterol-binding and actin-regulatory molecule MARCKS in the synapses of the hippocampus. This in turn leads to reduced clustering of the phosphoinositide PI(4,5)P2 for hydrolysis by PLCɣ and consequently in a reduced signaling towards the expression of learning and memory genes.
What is the impact of this study?
Carlos: For the moment it is just academic: we learnt about one of the molecular events participating in a particular deficit of the old: reduced hippocampal synaptic plasticity. It remains to be established whether or not an exaggeration of the biochemical deficits discovered in our work (eg. MARCKS/PIP2 loss), or an earlier occurrence of this deficit, plays a role in pathological brain aging.