The Diphasic Changes Of Alzheimer-like Tau Pathology And Space Memory Inducing By Flurocitrate And Its Underlying Mechanisms

Background Interactions between neurons and glial cells in the brain may serve important functions. Fast neuron-glia synaptic transmission has been found between hippocampal neurons and NG2 cells, a distinct population of microglia like cells widely distributed in the brain. These neuron-glia synapses undergo activity-dependent modifications analogous to long-term potentiation (LTP) at excitatory synapses, a hallmark of neuronal plasticity. Glial cells in the spinal dorsal horn play a role in the induction and maintenance of pathological pain due to inflammation and/or nerve injury. In Alzheimer's disease (AD), a wall of reactive astrocytes typically surrounds senile plaques ofβ-amyloid (Aβ).Astrocytes participate inβ-amyloid clearance and degradation, provide trophic support to neurons, and form a protective barrier between Aβdeposits and neurons. Functional hemichannels that have a role in glutamate homeostasis may significantly contribute to astrocyte-mediated regulation of neuronal activity. Fluorocitrate suggested selectively impaired astrocyte metabolism.Whether and how flurocitrate may cause AD-like tau hyperphosphorylation and space memory injury are not known.Objective To investigate damage of astrocyte leads to dysregulated neuronal by fluorocitrate treatment.Methods We investigated the synaptic transmission by measuring long term potentiation and spatial memory by measuring Morris water maze after fluorocitrate treatment. Tau phosphorylation, protein kinases and protein phosphatases and memory-related proteins were examined with western blotting after fluorocitrate treatment in primary astrocytes, primary neurons and rats. flurocitrate treatment in 1h, and tau dephosphorylation space memory improvement after fluorocitrate treatment in 48h. The activity of PP2A and AKT was decreased in 1h and were recovered in 48h after fluorocitrate treatment, which was similar with tau hyperphosphorylation in 1h and dephosphorylation in 48h after fluorocitrate treatment, and which were similar with LTP deficit in 1h and space memory improvement in 48h after fluorocitrate treatment. Fluorocitrate treatment causes LTP deficit in 1h and space memory improvemen in 48h by affecting multiple synapse-associated and other memory-associated proteins.Conclusion Astrocytes regulate space memory through regulating multiple synapse-associate proteins and Alzheimer-like tau phosphorylation.