Positive and negative early life experiences differentially modulate long term survival and amyloid protein levels in a mouse model of Alzheimer's disease

Lesuis, Sylvie L.; Maurin, Hervé; Borghgraef, Peter; Lucassen, Paul J.; Leuven, Fred Van; Krugers, Harm J.

doi:10.18632/oncotarget.9776

Cited by 51 publications

(51 citation statements)

References 83 publications

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“…Adult offspring from LBN mothers are more vulnerable to the development of stress-related dysfunctions, closely mimicking the exposure to a chronically stressful early environment in children. The effect of LBN might even be observed in ageing since overall survival, amyloid processing and Alzheimer pathology have been reported to be altered after LBN and adult stress in Alzheimer mouse models (Hoeijmakers et al, 2016; Lesuis et al, 2016). These effects of LBN may, at least in part involve inflammatory changes (Brunson, et al, 2005; Green, Billings, Roozendaal, McGaugh, & LaFerla, 2006; Hoeijmakers, Lucassen, & Korosi, 2015; Hoeijmakers, et al, 2016; Lesuis, et al, 2016).…”

Section: Proximal (Neonatal) and Distal (Adult) Phenotypes Resultimentioning

confidence: 99%

Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential

Walker

Bath

Joëls

et al. 2017

Stress

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The immediate and long term effects of exposure to early life stress (ELS) have been documented in humans and animal models. Even relatively brief periods of stress during the first 10 days of life in rodents can impact later behavioral regulation and the vulnerability to develop adult pathologies, in particular an impairment of cognitive functions and neurogenesis, but also modified social, emotional and conditioned fear responses. The development of preclinical models of ELS exposure allows the examination of mechanisms and testing of therapeutic approaches that are not possible in humans. Here we describe limited bedding and nesting (LBN) procedures, with models that produce altered maternal behavior ranging from fragmentation of care to maltreatment of infants. The purpose of this paper is to discuss important issues related to the implementation of this chronic ELS procedure and to describe some of the most prominent endpoints and consequences, focusing on areas of convergence between laboratories. Effects on the hypothalamic-pituitary adrenal (HPA) axis, gut axis and metabolism are presented in addition to changes in cognitive and emotional functions. Interestingly, recent data have suggested a strong sex difference in some of the reported consequences of the LBN paradigm, with females being more resilient in general than males. As both the chronic and intermittent variants of the LBN procedure have profound consequences on the offspring with minimal external intervention from the investigator, this model is advantageous ecologically and has a large translational potential. In addition to the direct effect of ELS on neurodevelopmental outcomes, exposure to adverse early environments can also have intergenerational impacts on mental health and function in subsequent generation offspring. Thus, advancing our understanding of the effect of ELS on brain and behavioral development is of critical concern for the health and wellbeing of both the current population, and for generations to come.

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Section: Proximal (Neonatal) and Distal (Adult) Phenotypes Resultimentioning

confidence: 99%

Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential

Walker

Bath

Joëls

et al. 2017

Stress

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273

322

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“…AD [11]. ES further triggers an earlier onset of Aβ plaques [12], and increases Aβ plaque load [12][13][14], which is accompanied by exacerbated cognitive impairment and shorter survival in AD mouse models [12,13,15,16], but see [17], where ES did not further exacerbate cognitive impairments, indicative of floor effects, which highlights the importance of the specific tasks, timing, and protocols performed.…”

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confidence: 96%

Characterization of astrocytes throughout life in wildtype and APP/PS1 mice after early-life stress exposure

Abbink

Kotah

Hoeijmakers

et al. 2020

J Neuroinflammation

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Background: Early-life stress (ES) is an emerging risk factor for later life development of Alzheimer's disease (AD). We have previously shown that ES modulates amyloid-beta pathology and the microglial response to it in the APPswe/PS1dE9 mouse model. Because astrocytes are key players in the pathogenesis of AD, we studied here if and how ES affects astrocytes in wildtype (WT) and APP/PS1 mice and how these relate to the previously reported amyloid pathology and microglial profile. Methods: We induced ES by limiting nesting and bedding material from postnatal days (P) 2-9. We studied in WT mice (at P9, P30, and 6 months) and in APP/PS1 mice (at 4 and 10 months) (i) GFAP coverage, cell density, and complexity in hippocampus (HPC) and entorhinal cortex (EC); (ii) hippocampal gene expression of astrocyte markers; and (iii) the relationship between astrocyte, microglia, and amyloid markers.Results: In WT mice, ES increased GFAP coverage in HPC subregions at P9 and decreased it at 10 months. APP/PS1 mice at 10 months exhibited both individual cell as well as clustered GFAP signals. APP/PS1 mice when compared to WT exhibited reduced total GFAP coverage in HPC, which is increased in the EC, while coverage of the clustered GFAP signal in the HPC was increased and accompanied by increased expression of several astrocytic genes. While measured astrocytic parameters in APP/PS1 mice appear not be further modulated by ES, analyzing these in the context of ES-induced alterations to amyloid pathology and microglial shows alterations at both 4 and 10 months of age.Conclusions: Our data suggest that ES leads to alterations to the astrocytic response to amyloid-β pathology.

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“…For example, ES in different rodent models modulates the aggregation of amyloid beta (Aβ), one of the neuropathological hallmarks of AD [11]. ES further triggers an earlier onset of Aβ plaques [12], and increases Aβ plaque load [12][13][14], which is accompanied by exacerbated cognitive impairment and shorter survival in AD mouse models [12,13,15,16], but see [17], where ES did not further exacerbate cognitive impairments, indicative of floor effects, which highlights the importance of the specific tasks, timing and protocols performed.…”

Section: Introductionmentioning

confidence: 99%

Characterization of astrocytes throughout life in wildtype and APP/PS1 mice after early-life stress exposure

Abbink¹,

Kotah²,

Hoeijmakers³

et al. 2020

Preprint

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Background Early-life stress (ES) is an emerging risk factor for later-life development of Alzheimer’s disease (AD). We have previously shown that ES modulates amyloid-beta pathology and the microglial response to it in the APPswe/PS1dE9 mouse model. Because astrocytes are key players in the pathogenesis of AD, we studied here if and how ES affects astrocytes in wildtype (WT) and APP/PS1 mice, and how these relate to the previously reported amyloid pathology and microglial profile. Methods We induced ES by limiting nesting and bedding material from postnatal days (P) 2-9. We studied in WT mice (at P9, P30 and 6 months) and in APP/PS1 mice (at 4 and 10 months) i) GFAP coverage, cell density and complexity in hippocampus (HPC) and entorhinal cortex (EC); ii) hippocampal gene expression of astrocyte markers; and iii) the relationship between astrocyte, microglia and amyloid markers. Results In WT mice, ES increased GFAP coverage in HPC subregions at P9, and decreased it at 10 months. APP/PS1 mice at 10 months exhibited both individual cell as well as clustered GFAP signals. APP/PS1 mice when compared to WT exhibited reduced total GFAP coverage in HPC, which is increased in the EC, while coverage of the clustered GFAP signal in the HPC was increased and accompanied by increased expression of several astrocytic genes. While measured astrocytic parameters in APP/PS1 mice appear not be further modulated by ES, analyzing these in the context of ES-induced alterations to amyloid pathology and microglial shows alterations at both 4 and 10 months of age. Conclusions Our data suggest that ES leads to alterations to the astrocytic response to amyloid-β pathology.

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Positive and negative early life experiences differentially modulate long term survival and amyloid protein levels in a mouse model of Alzheimer's disease

Cited by 51 publications

References 83 publications

Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential

Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential

Characterization of astrocytes throughout life in wildtype and APP/PS1 mice after early-life stress exposure

Characterization of astrocytes throughout life in wildtype and APP/PS1 mice after early-life stress exposure

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