An astrocytic basis of caloric restriction action on the brain plasticity

Abstract

One month of calorically restricted diet (CR) induced morphological plasticity of astrocytes in the stratum (str.) radiatum of hippocampal CA1 in three-months old mice: the volume fraction of distal perisynaptic astrocytic processes increased whereas the number of gap-junction coupled astrocytes decreased. The uncoupling was not associated with a decrease in the expression of connexin 43. Uncoupling and morphological remodeling affected spontaneous Ca2+ activity in the astrocytic network: Ca2+ events became longer, whereas their spread was reduced. The change in the pattern of astrocytic Ca2+ activity may increase the spatial resolution of the information encoding in the astroglial network. Consistent with expanded synaptic enwrapping by the astroglial processes, the spillover of synaptically released K+ and glutamate was diminished after CR. However, no significant changes in the expression of astrocytic glutamate transporter (GLT-1/EAAT2) were observed, although the level of glutamine synthetase was decreased. Glutamate uptake is known to regulate the synaptic plasticity. Indeed, the magnitude of long-term potentiation (LTP) in the glutamatergic CA3-CA1 synapses was significantly enhanced after CR. Our findings highlight an astroglial basis for improved learning and memory reported in various species subjected to CR.