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Objective Astrocytes play an important role in the homeostasis of Glu during excitatory information transmission in the CNS.Astrocytes could utilize the Glu transporters to remove Glu from the synaptic cleft.Inside astrocytes, the internalized Glu is utilized for glutamine synthesis through glutamine synthetase, or for energy production through the TCA cycle.However, we estimated that the total amount of Glu uptaken into astrocytes is much higher than the combined amount of Glu dedicated to glutamine synthesis and TCA cycle.This would result in an accumulation of Glu in the cytoplasm.Considering the vital roles of Glu as the most important signaling molecule in the CNS, it is unlikely that the cytoplasmic Glu remains dormant and merely waits to be metabolized.We reported that cytoplasmic Glu could enter nucleus and cause nuclear swelling.Methods Morphological changes on various cell types and their isolated nuclei were observed by phase contrast microscopy, fluorescence microscopy, confocal laser microscopy and atomic force microscopy.Antagonists and agonists of different Glu receptors, inhibitors of Glu transporters were used to study the mechanism of Glu-induced nuclear swelling in astrocyte.Localization of water channels including AQP1 in astrocyte was determined by RT-PCR, Western Blot, immunostaining and AQP1-EGFP transfection.Results Glu was found to specifically induce reversible nuclear swelling in astrocytes, but not in any other cell types and their isolated nuclei.This was a direct and specific effect limited to Glu but not other related compounds.Ammonia is metabolically related to Glu and could induce an indirect nuclear swelling in intact astrocytes but a direct shrinkage in isolated nuclei.Two unique features are required for this Glu-induced nuclear swelling: the Glu transporters on plasma membrane and the specific expression of AQP1 on the nuclear membrane of astrocytes.In addition, similar Glu-induced nuclear swelling and specific AQP1 nuclear localization were observed in human astrocytoma cells U251, and human astrocyte.Conclusion Glu released by neuron could induce specific effect on astrocytes nuclear size, indicating astrocytes could intone with neurons through Glu and the AQP 1 specifically localized on their nuclear membrane.