The APP670/671 mutation alters calcium signaling and response to hyperosmotic stress in rat primary hippocampal neurons

Kloskowska, Ewa; Bruton, Joseph D.; Winblad, Bengt; Benedikz, Eiríkur

doi:10.1016/j.neulet.2008.08.051

Cited by 8 publications

(4 citation statements)

References 17 publications

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“…The third stress condition we chose to investigate is hyperosmotic stress, leading to cell shrinkage and thereby inducing several cellular pathways as volume regulation and cytoskeletal reorganization. Hyperosmotic stress is also known to induce apoptosis (Kloskowska et al 2008) and seems to play a role in inflammatory processes (Brocker et al 2010). This stress condition is achieved by adding the osmotically active substance sorbitol to the medium which cannot be metabolized by the cell.…”

Section: Introductionmentioning

confidence: 99%

Reaction of small heat-shock proteins to different kinds of cellular stress in cultured rat hippocampal neurons

Bartelt-Kirbach

Golenhofen

2014

Cell Stress and Chaperones

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Upregulation of small heat-shock proteins (sHsps) in response to cellular stress is one mechanism to increase cell viability.We previously described that cultured rat hippocampal neurons express five of the 11 family members but only upregulate two of them (HspB1 and HspB5) at the protein level after heat stress. Since neurons have to cope with many other pathological conditions, we investigated in this study the expression of all five expressed sHsps on mRNA and protein level after sublethal sodium arsenite and oxidative and hyperosmotic stress. Under all three conditions, HspB1, HspB5, HspB6, and HspB8 but not HspB11 were consistently upregulated but showed differences in the time course of upregulation. The increase of sHsps always occurred earlier on mRNA level compared with protein levels. We conclude from our data that these four upregulated sHsps (HspB1, HspB5, HspB6, HspB8) act together in different proportions in the protection of neurons from various stress conditions.

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Section: Introductionmentioning

confidence: 99%

Reaction of small heat-shock proteins to different kinds of cellular stress in cultured rat hippocampal neurons

Bartelt-Kirbach

Golenhofen

2014

Cell Stress and Chaperones

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“…It is also well known that AD patients may have striking fluctuations in functional abilities even within the same day, which strongly implies that at least some of the neurological impairment is due to a dysfunction of neuronal networks rather than loss of neurons [34]. We have previously shown that primary neurons derived from the Tg6590 rats have increased intracellular calcium levels and altered calcium signalling which is indicative of aberrant neuronal activation [35–36] and could underlie the observed memory impairment.…”

Section: Discussionmentioning

confidence: 99%

Cognitive impairment in the Tg6590 transgenic rat model of Alzheimer’s disease

Kloskowska

Pham

Nilsson

et al. 2010

J Cellular Molecular Medi

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Recently, interest in the rat as an animal model of Alzheimer’s disease (AD) has been growing. We have previously described the Tg6590 transgenic rat line expressing the amyloid precursor protein containing the Swedish AD mutation (K670M/N671L) that shows early stages of Aβ deposition, predominantly in cerebrovascular blood vessels, after 15 months of age. Here we show that by the age of 9 months, that is long before the appearance of Aβ deposits, the Tg6590 rats exhibit deficits in the Morris water maze spatial navigation task and altered spontaneous behaviour in the open-field test. The levels of soluble Aβ were elevated both in the hippocampus and cortex of transgenic animals. Magnetic resonance imaging showed no major changes in the brains of transgenic animals, although they tended to have enlarged lateral ventricles when compared to control animals. The Tg6590 transgenic rat line should prove a suitable model of early AD for advanced studies including serial cerebrospinal fluid sampling, electrophysiology, neuroimaging or complex behavioural testing.

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“…Similar to the UKUR25 line, there is an apparent increase in phosphorylated tau at the PHF‐1 site in the Tg6590 rat brain, but the increase does not reach statistical significance. Cultured primary hippocampal neurons from this line show complex alterations of calcium homeostasis, that could potentially play a role in the learning and memory impairments seen in these animals [95, 96]. Although the Tg6590 line needs to be further characterized in terms of onset and progression of behavioural phenotypes, it represents a promising model for advanced behavioural studies.…”

Section: Transgenic Ratsmentioning

confidence: 99%

“…Similar to the UKUR25 line, there is an apparent increase in phosphorylated tau at the PHF-1 site in the Tg6590 rat brain, but the increase does not reach statistical significance. Cultured primary hippocampal neurons from this line show complex alterations of calcium homeostasis, that could potentially play a role in the learning and memory impairments seen in these animals [95,96]. Although the Tg6590 [102,104] APPswe, APP with the 'Swedish' K670N/M671L mutation; APPind, V717F 'Indiana' mutation; PS1 Finn, PS1 with the M146L Finnish mutation; hTau truncated, human tau truncated at amino acid positions 151-391; PDGF, platelet-derived growth factor; PrP, prion promoter; Thy1, Thymocyte differentiation antigen 1 promoter; P-tau, phosphorylated tau immunoreactivity; SHR, spontaneously hypertensive rat; Nr, not reported.…”

Section: The Ukur25 Ratmentioning

confidence: 99%

The rat as an animal model of Alzheimer's disease

Benedikz

Kloskowska

Winblad

2009

J Cellular Molecular Medi

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As a disease model, the laboratory rat has contributed enormously to neuroscience research over the years. It has also been a popular animal model for Alzheimer’s disease but its popularity has diminished during the last decade, as techniques for genetic manipulation in rats have lagged behind that of mice. In recent years, the rat has been making a comeback as an Alzheimer’s disease model and the appearance of increasing numbers of transgenic rats will be a welcome and valuable complement to the existing mouse models. This review summarizes the contributions and current status of the rat as an animal model of Alzheimer’s disease.

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The APP670/671 mutation alters calcium signaling and response to hyperosmotic stress in rat primary hippocampal neurons

Cited by 8 publications

References 17 publications

Reaction of small heat-shock proteins to different kinds of cellular stress in cultured rat hippocampal neurons

Reaction of small heat-shock proteins to different kinds of cellular stress in cultured rat hippocampal neurons

Cognitive impairment in the Tg6590 transgenic rat model of Alzheimer’s disease

The rat as an animal model of Alzheimer's disease

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