Dataset Information

Hippocampal neurons in direct contact with astrocytes exposed to amyloid ?_25-35 exhibit reduced excitatory synaptic transmission.

ABSTRACT: Amyloid ? protein (A?) is closely related to the progression of Alzheimer's disease because senile plaques consisting of A? 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 A? fragment 25-35 (A?_25-35) affect synaptic transmission. We show that synaptic transmission by hippocampal neurons was inhibited by astrocytes exposed to A?_25-35. The A?_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 A?_25-35-exposed astrocytes and hippocampal neurons. These data indicate that direct contact between A?_25-35-exposed astrocytes and neurons is critical for inhibiting synaptic transmission in the progression of Alzheimer's disease.

SUBMITTER: Oyabu K

PROVIDER: S-EPMC6669318 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Hippocampal neurons in direct contact with astrocytes exposed to amyloid β<sub>25-35</sub> exhibit reduced excitatory synaptic transmission.

Oyabu Kohei K Kiyota Hiroki H Kubota Kaori K Watanabe Takuya T Katsurabayashi Shutaro S Iwasaki Katsunori K

IBRO reports 20190723

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<sub>25-35</sub>) affect synaptic transmission. We show that synaptic transmission by hippocamp ...[more]

PMID: 31388597

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Project description:Blast traumatic brain injury (bTBI) affects civilians, soldiers, and veterans worldwide and presents significant health concerns. The mechanisms of neurodegeneration following bTBI remain elusive and current therapies are largely ineffective. It is important to better characterize blast-evoked cellular changes and underlying mechanisms in order to develop more effective therapies. In the present study, our group utilized rat organotypic hippocampal slice cultures (OHCs) as an in vitro system to model bTBI. OHCs were exposed to either 138 ± 22 kPa (low) or 273 ± 23 kPa (high) overpressures using an open-ended helium-driven shock tube, or were assigned to sham control group. At 2 hours (h) following injury, we have characterized the astrocytic response to a blast overpressure. Immunostaining against the astrocytic marker glial fibrillary acidic protein (GFAP) revealed acute shearing and morphological changes in astrocytes, including clasmatodendrosis. Moreover, overlap of GFAP immunostaining and propidium iodide (PI) indicated astrocytic death. Quantification of the number of dead astrocytes per counting area in the hippocampal cornu Ammonis 1 region (CA1), demonstrated a significant increase in dead astrocytes in the low- and high-blast, compared to sham control OHCs. However only a small number of GFAP-expressing astrocytes were co-labeled with the apoptotic marker Annexin V, suggesting necrosis as the primary type of cell death in the acute phase following blast exposure. Moreover, western blot analyses revealed calpain mediated breakdown of GFAP. The dextran exclusion additionally indicated membrane disruption as a potential mechanism of acute astrocytic death. Furthermore, although blast exposure did not evoke significant changes in glutamate transporter 1 (GLT-1) expression, loss of GLT-1-expressing astrocytes suggests dysregulation of glutamate uptake following injury. Our data illustrate the profound effect of blast overpressure on astrocytes in OHCs at 2 h following injury and suggest increased calpain activity and membrane disruption as potential underlying mechanisms.

Dataset Information

Hippocampal neurons in direct contact with astrocytes exposed to amyloid ?_25-35 exhibit reduced excitatory synaptic transmission.

Publications

Hippocampal neurons in direct contact with astrocytes exposed to amyloid β<sub>25-35</sub> exhibit reduced excitatory synaptic transmission.

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Dataset Information

Hippocampal neurons in direct contact with astrocytes exposed to amyloid ?25-35 exhibit reduced excitatory synaptic transmission.

Publications

Hippocampal neurons in direct contact with astrocytes exposed to amyloid β<sub>25-35</sub> exhibit reduced excitatory synaptic transmission.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Hippocampal neurons in direct contact with astrocytes exposed to amyloid ?_25-35 exhibit reduced excitatory synaptic transmission.