Hippocampal neurons in direct contact with astrocytes exposed to amyloid β25-35 exhibit reduced excitatory synaptic transmission

Kohei Oyabu; Hiroki Kiyota; Kaori Kubota; Takuya Watanabe; Shutaro Katsurabayashi; Katsunori Iwasaki

doi:10.1016/j.ibror.2019.07.1719

Hippocampal neurons in direct contact with astrocytes exposed to amyloid β_25-35 exhibit reduced excitatory synaptic transmission

IBRO Rep. 2019 Jul 23:7:34-41. doi: 10.1016/j.ibror.2019.07.1719. eCollection 2019 Dec.

Authors

Kohei Oyabu¹, Hiroki Kiyota¹, Kaori Kubota^{1

2}, Takuya Watanabe^{1

2}, Shutaro Katsurabayashi¹, Katsunori Iwasaki^{1

2}

Affiliations

¹ Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
² A.I.G. Collaborative Research Institute for Aging and Brain Sciences, Fukuoka University, Fukuoka, Japan.

Abstract

Amyloid β protein (Aβ) is closely related to the progression of Alzheimer's disease because senile plaques consisting of Aβ cause synaptic depression and synaptic abnormalities. In the central nervous system, astrocytes are a major glial cell type that contribute to the modulation of synaptic transmission and synaptogenesis. In this study, we examined whether astrocytes exposed to Aβ fragment 25-35 (Aβ_25-35) affect synaptic transmission. We show that synaptic transmission by hippocampal neurons was inhibited by astrocytes exposed to Aβ_25-35. The Aβ_25-35-exposed astrocytes lowered excitatory postsynaptic release and the size of the readily releasable synaptic pool. The number of excitatory synapses was also reduced. However, the number of excitatory synapses was unchanged unless there was direct contact between Aβ_25-35-exposed astrocytes and hippocampal neurons. These data indicate that direct contact between Aβ_25-35-exposed astrocytes and neurons is critical for inhibiting synaptic transmission in the progression of Alzheimer's disease.

Keywords: Alzheimer’s disease; Astrocytes; Aβ; Synaptic release.