Fluorocitrate induced the alterations of memory-related proteins and tau hyperphosphorylation in SD rats.

Astrocytes provide structural, metabolic and trophic supports for neurons. However, there are no direct evidences whether astrocytes involve in the regulation of synaptic proteins expression and tau phosphorylation until now. Here, we injected 1 nmol fluorocitrate (FC), which preferentially taken up by astrocytes and results in reversible inhibition of the astrocytic tricarboxylic acid cycle, into the left lateral ventricle of the brain in the SD rats for 1h, and found that FC treatment decreased several memory-related proteins levels, such as AMPA receptor GluR1/2, postsynaptic density protein 93/95, Arc and phosphorylated cAMP response element binding proteins, while increased synaptophysin and synapsin I levels in the hippocampus. FC treatment also increased the levels of phosphorylated tau at multiple Alzheimer-related phosphorylation sites, as well as activation of glycogen synthase kinase-3β and inactivation of protein phosphatase-2A. Similar effects were also observed in the primary hippocampal neurons, which were cultured with the conditioned media from FC-treatment primary astrocytes. Our data suggest that astrocytes regulate neuronal tau phosphorylation and several synaptic proteins expression.