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Brain Res. 2018 Jan 1;1678:129-137. doi: 10.1016/j.brainres.2017.10.011. Epub 2017 Oct 21.

Astrocytic glutamatergic transporters are involved in Aβ-induced synaptic dysfunction.

Author information

1
Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China.
2
Clinical Medicine Research Centre, Shunde Hospital, Southern Medical University, Foshan, Guangdong 528300, China; Department of Neurology, Shunde Hospital, Southern Medical University, Foshan, Guangdong 528300, China.
3
Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China; Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, China.
4
Teaching Center of Experimental Medicine, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China.
5
Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510082, China.
6
State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China.
7
Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China; State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China.
8
Department of Neurology, The Third Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, China.
9
Department of Geroatric&Neurology, Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
10
Clinical Medicine Research Centre, Shunde Hospital, Southern Medical University, Foshan, Guangdong 528300, China; Department of Neurology, Shunde Hospital, Southern Medical University, Foshan, Guangdong 528300, China. Electronic address: sgq9528@163.com.
11
Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China; Ann Romney Center for Neurologic Disease, Brigham and Women's Hospital of Harvard Medical School, Boston, MA 02115, USA. Electronic address: shaomin_li@hms.harvard.edu.
12
Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China. Electronic address: pingyixu@sina.com.

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.

KEYWORDS:

Alzheimer’s disease; Astrocytes; Glutamate transporters; Long-term potentiation; Synaptic plasticity; TBOA

PMID:
29066369
DOI:
10.1016/j.brainres.2017.10.011
[Indexed for MEDLINE]

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