Abstract
Calorie-restricted (CR) diet has multiple beneficial effects on brain function. Here we report morphological and functional changes in hippocampal astrocytes in 3-months-old mice subjected to 1 month of the diet. Whole-cell patch-clamp recordings were performed in the CA1 stratum (str.) radiatum astrocytes of hippocampal slices. The cells were also loaded with fluorescent dye through the patch pipette. CR did not affect the number of astrocytic branches but increased the volume fraction (VF) of distal perisynaptic astrocytic leaflets. The astrocyte growth did not lead to a decrease in the cell input resistance, which may be attributed to a decrease in astrocyte coupling through the gap junctions. Western blotting revealed a decrease in the expression of Cx43 but not Cx30. Immunocytochemical analysis demonstrated a decrease in the density and size of Cx43 clusters. Cx30 cluster density did not change, while their size increased in the vicinity of astrocytic soma. CR shortened K+ and glutamate transporter currents in astrocytes in response to 5 × 50 Hz Schaffer collateral stimulation. However, no change in the expression of astrocytic glutamate transporter 1 (GLT-1) was observed, while the level of glutamine synthetase (GS) decreased. These findings suggest that enhanced enwrapping of synapses by the astrocytic leaflets reduces glutamate and K+ spillover. Reduced spillover led to a decreased contribution of extrasynaptic N2B containing N-methyl-D-aspartate receptors (NMDARs) to the tail of burst-induced EPSCs. The magnitude of long-term potentiation (LTP) in the glutamatergic CA3–CA1 synapses was significantly enhanced after CR. This enhancement was abolished by N2B-NMDARs antagonist. Our findings suggest that astrocytic morphofunctional remodeling is responsible for enhanced synaptic plasticity, which provides a basis for improved learning and memory reported after CR.
Highlights
Food consumption and dieting, as well as lifestyle and physical exercises, are essential determinants of lifespan as well as cognitive capabilities[1]
calorie restriction (CR) increases volume fraction (VF) of astrocytic leaflets Individual protoplasmic astrocytes were loaded with a fluorescent tracer Alexa Fluor 594 through a patch pipette and imaged with a two-photon laser scanning microscope in CA1 stratum radiatum of hippocampal slices
This approach assumes that soma fluorescence reflects 100% of astrocyte space occupancy, while the fluorescence of unresolved area is proportional to the VF of astrocyte processes in this area (Fig. 1c)
Summary
As well as lifestyle and physical exercises, are essential determinants of lifespan as well as cognitive capabilities[1]. A prominent positive effect of calorie restriction (CR) on the lifespan of rats was discovered in 19352, and have been confirmed since for Restrictive dieting affects brain aging; low-calorie intake has been noted to exert neuroprotection, retard agedependent cognitive decline, and decrease the incidence of neurodegenerative diseases[7]. Insufficient cognitive engagement, lack of exercise, and excessive food intake promote, whereas cognitive stimulation, physical activity and dieting delay age-dependent cognitive deterioration[5,10]. CR prevents an age-dependent decline in hippocampal synaptic plasticity[16], enhances neurogenesis[17], and improves neuronal plasticity in visual cortex[18] through increasing intracortical inhibition by upregulation of GABA synthesis and neuronal GABA content[19]. Whether CR causes such brain shrinkage, or it naturally occurs with aging beyond the average lifespan remains to be established
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