Amyloid-β peptide activates cultured astrocytes: morphological alterations, cytokine induction and nitric oxide release

Hu, Juan; Akama, Keith T.; Krafft, Grant A.; Chromy, Brett A.; Eldik, Linda J. Van

doi:10.1016/s0006-8993(97)01318-8

Cited by 301 publications

(201 citation statements)

References 45 publications

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“…In contrast, adhesion of astrocytes and microglia to nfA␤ is not well established. Previous reports have only shown that nonfibrillar oligomeric A␤-(1-42) was able to trigger glial activation, which can lead to the production of potentially toxic molecules, such as inflammatory cytokines (interleukin-1␤) and nitric oxide (49). It is interesting that glial cells adhered to nfA␤, because nfA␤ can spontaneously form insoluble assemblies of ␤-pleated sheets (fibrillar) similar to the amyloid fibrils found in AD brains.…”

Section: Discussionmentioning

confidence: 99%

Expression of Scavenger Receptors in Glial Cells

Alarcón

Fuenzalida

Santibáñez

et al. 2005

Journal of Biological Chemistry

142

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Section: Discussionmentioning

confidence: 99%

Expression of Scavenger Receptors in Glial Cells

Alarcón

Fuenzalida

Santibáñez

et al. 2005

Journal of Biological Chemistry

142

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“…A␤ oligomers have been demonstrated to cause these pathological changes in vitro when applied exogenously to cultured cells and brain slices (Hu et al, 1998;Lambert et al, 1998;Kayed et al, 2003;De Felice et al, 2008;Jimenez et al, 2008). However, it is still unclear whether A␤ oligomers have similar pathological effects in vivo.…”

Section: Abnormal Tau Phosphorylation In App E693⌬ -Tg Micementioning

confidence: 99%

“…Several studies have demonstrated that exogenously applied A␤ oligomers induce tau hyperphosphorylation (De Felice et al, 2008), activate astrocytes (Hu et al, 1998) and microglia (Jimenez et al, 2008), and cause neuronal death (Lambert et al, 1998; in vitro. However, in animal models, these findings have never been observed before amyloid plaque deposition (for review, see Duyckaerts et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

A Mouse Model of Amyloid β Oligomers: Their Contribution to Synaptic Alteration, Abnormal Tau Phosphorylation, Glial Activation, and Neuronal LossIn Vivo

Tomiyama¹,

Matsuyama²,

Iso³

et al. 2010

J. Neurosci.

352

367

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Although amyloid ␤ (A␤) oligomers are presumed to cause synaptic and cognitive dysfunction in Alzheimer's disease (AD), their contribution to other pathological features of AD remains unclear. To address the latter, we generated APP transgenic mice expressing the E693⌬ mutation, which causes AD by enhanced A␤ oligomerization without fibrillization. The mice displayed age-dependent accumulation of intraneuronal A␤ oligomers from 8 months but no extracellular amyloid deposits even at 24 months. Hippocampal synaptic plasticity and memory were impaired at 8 months, at which time the presynaptic marker synaptophysin began to decrease. Furthermore, we detected abnormal tau phosphorylation from 8 months, microglial activation from 12 months, astrocyte activation from 18 months, and neuronal loss at 24 months. These findings suggest that A␤ oligomers cause not only synaptic alteration but also other features of AD pathology and that these mice are a useful model of A␤ oligomer-induced pathology in the absence of amyloid plaques.

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“…As observed by Pfrieger and Barres 36 , neurons co-cultured with astrocytes develop www.scienceasia.org approximately 7-fold more synapses and have a 7-fold increase in synaptic efficacy compared with neurons raised in the absence of astrocytes. Astrocytes could contribute to neurodegeneration, as Aβ-activated astrocytes overexpress factors such as interleukin 1β, nitric oxide, and S100β [37][38][39] , which are all potentially neurotoxic 35 . In summary, our findings show that the reduction of cell viability is more prominent in mixed cell cultures (P < 0.001) than neuronal cell cultures (P < 0.05) when exposed to Aβ.…”

Section: Discussionmentioning

confidence: 99%

Untitled

Buntup¹,

Chayasadom²,

Surarit³

et al. 2009

ScienceAsia

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ABSTRACT:Alzheimer's disease is a major neurodegenerative disorder in which there is an overproduction and accumulation of amyloid-β (Aβ) peptides. During the initial stages of the disease, glutamate receptors are dysregulated by Aβ accumulation resulting in the disruption of glutamatergic synaptic transmission. We used rat cortical cell cultures to examine the effects of Aβ(25-35)-induced neurotoxicity on glutamine transporters involved in the glutamate cycle. In primary mixed cell cultures prepared from cerebral cortex, incubation with 10 µM Aβ(25-35) for 12 h, but not for 24 h, markedly suppressed system A transporter 1 (SAT1) mRNA expression. On the other hand, Aβ(25-35) had no effect on SAT1 mRNA level in neuronal cell cultures. Treatment of both types of cell cultures with Aβ(25-35) resulted in a significant decrease in cell survival in a concentration and time-dependent manner, as determined by MTT assay. These results indicated that Aβ may impair neuronal function and transmitter synthesis and perhaps reduce excitotoxicity through a reduction in neuronal glutamine uptake.

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Amyloid-β peptide activates cultured astrocytes: morphological alterations, cytokine induction and nitric oxide release

Cited by 301 publications

References 45 publications

Expression of Scavenger Receptors in Glial Cells

Expression of Scavenger Receptors in Glial Cells

A Mouse Model of Amyloid β Oligomers: Their Contribution to Synaptic Alteration, Abnormal Tau Phosphorylation, Glial Activation, and Neuronal LossIn Vivo

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