The effects of amyloid-β42 oligomer on the proliferation and activation of astrocytes in vitro

Abstract

Previous studies reported that astrocyte response to amyloid-β (Aβ) before obvious neuronal damage could be detected in Alzheimer's disease (AD). It is suggested that astrocytes play a key role in AD pathologies. In this study, we investigated the effects of Aβ(42) oligomer on the proliferation and activation of astrocytes by in vitro experiments. The results showed that Aβ(42) oligomers could convert astrocytes to responsive astrocytes. It was revealed by MTT and ELISA assays that the viability of astrocytes gradually decreased, and the release of brain-derived neurotrophic factor increased with elevated Aβ(42) concentration and prolonged duration. Reverse-transcription polymerase chain reaction (RT-PCR) assay indicated that Aβ(42) oligomers increased the expression of glial fibers acid protein and interleukin-1β in a dose-dependent but not time-dependent manner. It was showed that A8, a mouse monoclonal antibody, was able to protect the cultured astrocytes against the toxicity of Aβ(42) oligomers. The result demonstrated that A8 could inhibit Aβ(42) oligomers toxic effects on astrocytes and that, alone, A8 could promote the proliferation of astrocytes in certain time. The present study laid a theoretical foundation for further understanding the effects of Aβ(42) on astrocytes and, hence, is conducive to the theoretical understanding and clinical therapies of AD progression.

Metabolic changes and inflammation in cultured astrocytes from the 5xFAD mouse model of Alzheimer’s disease: Alleviation by pantethine

“…At this point, the increased levels of full length APP found in Tg astrocytes could account for increased levels of Aß and/or C99, but we failed to observe any difference between genotypes concerning these APP metabolites. In any case, our astrocytes are responsive to changes in Aß, since exposure to exogenous oAβ, increased astrocyte reactivity in both Tg and WT cells, in agreement with previous reports showing that Aβ causes astrocyte activation [26,29]. …”

“…We explored the alterations in energy metabolism and the inflammatory response of these astrocytes, with or without exposure to oligomeric Aβ (oAβ). The latter is known to stimulate astrocyte reactivity and initiate neuronal damage [26,27]. We determined the subsequent alterations in the glycolytic pathway and TCA cycle, as well as proteasome activity and the levels of HIF-1α, which has been reported to be neuroprotective in AD [28] and to reduce astrocyte activation after Aβ treatment [29,30].…”

NMR metabolomic investigation of astrocytes interacted with Aβ42 or its complexes with either copper(II) or zinc(II)

“…Such stress is reflected by a large decrease of intracellular calcium and by a similarly large increase of cell viability. Our results agree with other studies correlating augmented cell viability induced by Aβ to astrocyte activation [49][50][51] further supporting the idea that Aβ deposits make reactive astrocytes and modify their functions related to calcium homeostasis and connectivity [52,53]. Growing body of evidence suggests that the deregulation of brain calcium homeostasis facilitates the development and progression of AD [54].…”

Neuroinflammation and related neuropathologies in APPSL mice: further value of this in vivomodel of Alzheimer’s disease

“…Intriguingly, early microgliosis promotes Aβ clearance by protofibrillar Aβ phagocytosis [6,7], whereas chronic microgliosis seems to promote Aβ accumulation and subsequent neurodegeneration [6]. Astrogliosis, similar to microgliosis, can be caused by Aβ fibrils or oligomers [8,9]. Transplanted murine adult and neonatal astrocytes are able to internalize and degrade aggregated human Aβ in the hippocampi of APP transgenic mice, and can thus serve as active Aβ clearing cells [10].…”