Vitamin E increases S100B‐mediated microglial activation in an S100B‐overexpressing mouse model of pathological aging

Bialowas‐McGoey, Lynn A.; Lesicka, Agnieszka; Whitaker‐Azmitia, Patricia M.

doi:10.1002/glia.20727

Cited by 25 publications

(21 citation statements)

References 104 publications

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“…54 Inhibition of S100B has positive effects on the A β load and gliosis observed in AD patients, 55 whereas S100B overexpression has been associated with exacerbation of AD clinical signs. 56, 57 Finally, altered expression of cell cycle proteins (i.e., CCND3 ) in postmitotic neurons has been observed both in aging and in AD.…”

Section: Discussionmentioning

confidence: 99%

Early and sustained altered expression of aging-related genes in young 3xTg-AD mice

et al. 2014

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Alzheimer's disease (AD) is a multifactorial neurological condition associated with a genetic profile that is still not completely understood. In this study, using a whole gene microarray approach, we investigated age-dependent gene expression profile changes occurring in the hippocampus of young and old transgenic AD (3xTg-AD) and wild-type (WT) mice. The aim of the study was to assess similarities between aging- and AD-related modifications of gene expression and investigate possible interactions between the two processes. Global gene expression profiles of hippocampal tissue obtained from 3xTg-AD and WT mice at 3 and 12 months of age (m.o.a.) were analyzed by hierarchical clustering. Interaction among transcripts was then studied with the Ingenuity Pathway Analysis (IPA) software, a tool that discloses functional networks and/or pathways associated with sets of specific genes of interest. Cluster analysis revealed the selective presence of hundreds of upregulated and downregulated transcripts. Functional analysis showed transcript involvement mainly in neuronal death and autophagy, mitochondrial functioning, intracellular calcium homeostasis, inflammatory response, dendritic spine formation, modulation of synaptic functioning, and cognitive decline. Thus, overexpression of AD-related genes (such as mutant APP, PS1, and hyperphosphorylated tau, the three genes that characterize our model) appears to favor modifications of additional genes that are involved in AD development and progression. The study also showed overlapping changes in 3xTg-AD at 3 m.o.a. and WT mice at 12 m.o.a., thereby suggesting altered expression of aging-related genes that occurs earlier in 3xTg-AD mice.

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Section: Discussionmentioning

confidence: 99%

Early and sustained altered expression of aging-related genes in young 3xTg-AD mice

et al. 2014

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“…The membrane was incubated with a primary antibody (Ab) against RAGE (1:2000, Thermo Scientific, Waltham, MA, USA, 45 kDa), which was used to detect the RAGE signal of the brain in previous studies. 19, 20 Following primary incubation, blots were incubated with the horseradish peroxidase-conjugated secondary Ab (1:2000, Cell Signaling, Danvers, MA, USA). Blots were visualized using an enhanced chemiluminescence system and developed using Hyperfilm (Amersham, Piscataway, NJ, USA).…”

Section: Methodsmentioning

confidence: 99%

Increased expression of the receptor for advanced glycation end products in neurons and astrocytes in a triple transgenic mouse model of Alzheimer’s disease

Choi¹,

Cho²,

Kim³

et al. 2014

Exp Mol Med

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The receptor for advanced glycation end products (RAGE) has been reported to have a pivotal role in the pathogenesis of Alzheimer's disease (AD). This study investigated RAGE levels in the hippocampus and cortex of a triple transgenic mouse model of AD (3xTg-AD) using western blotting and immunohistochemical double-labeling to assess cellular localization. Analysis of western blots showed that there were no differences in the hippocampal and cortical RAGE levels in 10-month-old adult 3xTg-AD mice, but significant increases in RAGE expression were found in the 22- to 24-month-old aged 3xTg-AD mice compared with those of age-matched controls. RAGE-positive immunoreactivity was observed primarily in neurons of aged 3xTg-AD mice with very little labeling in non-neuronal cells, with the notable exception of RAGE presence in astrocytes in the hippocampal area CA1. In addition, RAGE signals were co-localized with the intracellular amyloid precursor protein (APP)/amyloid beta (Aβ) but not with the extracellular APP/Aβ. In aged 3xTg-AD mice, expression of human tau was observed in the hippocampal area CA1 and co-localized with RAGE signals. The increased presence of RAGE in the 3xTg-AD animal model showing critical aspects of AD neuropathology indicates that RAGE may contribute to cellular dysfunction in the AD brain.

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“…However, these positive effects may be modulated in a full HSA21q trisomy by contributions of the S100B protein. S100B is a Ca 2+ -binding protein whose function is regulated by oxidative state, promoting neuronal survival in the oxidized state and apoptosis and neurotoxicity in the reduced state [62]. A transgenic mouse that overexpresses S100B displays learning and memory impairment and increased levels of apoptotic markers, but treatment of this mouse with vitamin E increased oxidative damage.…”

Section: Approaches To Pharmacotherapeutic Target Identificationmentioning

confidence: 99%

Molecular basis of pharmacotherapies for cognition in Down syndrome

Gardiner

2010

Trends in Pharmacological Sciences

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Intellectual disability (ID) in Down syndrome (DS) ranges from low normal to severely impaired, and has a significant impact on the quality of life of the individuals affected and their families. Because the incidence of DS remains at approximately one in 700 live births and the life span is now >50 years, development of pharmacotherapies for cognitive deficits is an important goal. DS is due to an extra copy of human chromosome 21 and has often been considered too complex a genetic abnormality to be amenable to intervention. However, recent successes in rescuing learning/memory impairments in a mouse model of DS suggest that this negative outlook may not be justified. In this article, we first review the DS phenotype, chromosome 21 gene content and mouse models, and then discuss recent successes and remaining challenges in the identification of targets for and preclinical evaluation of potential therapeutics.

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Vitamin E increases S100B‐mediated microglial activation in an S100B‐overexpressing mouse model of pathological aging

Cited by 25 publications

References 104 publications

Early and sustained altered expression of aging-related genes in young 3xTg-AD mice

Early and sustained altered expression of aging-related genes in young 3xTg-AD mice

Increased expression of the receptor for advanced glycation end products in neurons and astrocytes in a triple transgenic mouse model of Alzheimer’s disease

Molecular basis of pharmacotherapies for cognition in Down syndrome

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