Astrocytic glutamatergic transporters are involved in A β-induced synaptic dysfunction.

Astrocytic glutamatergic transporters are involved in Aβ-induced synaptic dysfunction.
Brain Res. 2017 Oct 21;:
Authors: Huang S, Tong H, Lei M, Zhou M, Guo W, Li G, Tang X, Li Z, Mo M, Zhang X, Chen X, Cen L, Wei L, Xiao Y, Li K, Huang Q, Yang X, Liu W, Zhang L, Qu S, Li S, Xu P
Abstract
In Alzheimer's disease (AD), dementia severity correlates most strongly with decreased synapse density in the hippocampus and cerebral cortex. Although studies in rodents have established that hippocampal long-term potentiation (LTP) is inhibited by soluble oligomers of beta-amyloid (Aβ), the synaptic mechanisms remain unclear. Here, field excitatory postsynaptic potentials (fEPSP) recordings were made in the CA1 region of mouse hippocampal slices. The medium of APP-expressing CHO cells, which contain soluble forms of Aβ including small oligomers, inhibited LTP and facilitated long-term depression (LTD), thus making the LTP/LTD curve shift toward the right. This phenomenon could be mimicked by the non-selective glutamate transporter inhibitor, DL-TBOA. More specifically, the Aβ impaired LTP and facilitated LTD were occluded by the selective astrocytic glutamate transporter inhibitors, TFB-TBOA. In cultured astrocytes, the Aβ oligomers also decrease astrocytic glutamate transporters (EAAT1, EAAT2) expression. We conclude that soluble Aβ oligomers decrease the activation of astrocytic glutamate transporters, thereby impairing synaptic plasticity...

Source: Brain Research - October 21, 2017 Category: Neurology Authors: Huang S, Tong H, Lei M, Zhou M, Guo W, Li G, Tang X, Li Z, Mo M, Zhang X, Chen X, Cen L, Wei L, Xiao Y, Li K, Huang Q, Yang X, Liu W, Zhang L, Qu S, Li S, Xu P Tags: Brain Res Source Type: research