scholarly journals Transcriptomic Insights into the Response of the Olfactory Bulb to Selenium Treatment in a Mouse Model of Alzheimer’s Disease

2019 ◽  
Vol 20 (12) ◽  
pp. 2998 ◽  
Author(s):  
Rui Zheng ◽  
Zhong-Hao Zhang ◽  
Yu-Xi Zhao ◽  
Chen Chen ◽  
Shi-Zheng Jia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Olfactory Bulb ◽  
Neurodegenerative Disorder ◽  
Therapeutic Option ◽  
Senile Plaques ◽  
Tau Proteins ◽  
Therapeutic Effects ◽  
Model Of Alzheimer’S Disease

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by the presence of extracellular senile plaques primarily composed of Aβ peptides and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau proteins. Olfactory dysfunction is an early clinical phenotype in AD and was reported to be attributable to the presence of NFTs, senile Aβ plaques in the olfactory bulb (OB). Our previous research found that selenomethionine (Se-Met), a major form of selenium (Se) in organisms, effectively increased oxidation resistance as well as reduced the generation and deposition of Aβ and tau hyperphosphorylation in the olfactory bulb of a triple transgenic mouse model of AD (3×Tg-AD), thereby suggesting a potential therapeutic option for AD. In this study, we further investigated changes in the transcriptome data of olfactory bulb tissues of 7-month-old triple transgenic AD (3×Tg-AD) mice treated with Se-Met (6 µg/mL) for three months. Comparison of the gene expression profile between Se-Met-treated and control mice revealed 143 differentially expressed genes (DEGs). Among these genes, 21 DEGs were upregulated and 122 downregulated. The DEGs were then annotated against the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The results show that upregulated genes can be roughly classified into three types. Some of them mainly regulate the regeneration of nerves, such as Fabp7, Evt5 and Gal; some are involved in improving cognition and memory, such as Areg; and some are involved in anti-oxidative stress and anti-apoptosis, such as Adcyap1 and Scg2. The downregulated genes are mainly associated with inflammation and apoptosis, such as Lrg1, Scgb3a1 and Pglyrp1. The reliability of the transcriptomic data was validated by quantitative real time polymerase chain reaction (qRT-PCR) for the selected genes. These results were in line with our previous study, which indicated therapeutic effects of Se-Met on AD mice, providing a theoretical basis for further study of the treatment of AD by Se-Met.

scholarly journals Neurogenesis, Neurodegeneration, Interneuron Vulnerability, and Amyloid-β in the Olfactory Bulb of APP/PS1 Mouse Model of Alzheimer's Disease

2016 ◽  
Vol 10 ◽  
Author(s):  
Carlos De la Rosa-Prieto ◽  
Daniel Saiz-Sanchez ◽  
Isabel Ubeda-Banon ◽  
Alicia Flores-Cuadrado ◽  
Alino Martinez-Marcos
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Olfactory Bulb ◽  
Amyloid Β ◽  
Model Of Alzheimer’S Disease

P3-047: Analysis of tau protein and amyloid-b expression in the olfactory bulb of the triple transgenic mouse model of Alzheimer's disease

2015 ◽  
Vol 11 (7S_Part_14) ◽  
pp. P636-P636
Author(s):  
Claudia Luna-Herrera ◽  
Azucena Vázquez-Aguilar ◽  
Maria del Carmen Cardenas-Aguayo ◽  
Fidel de la Cruz-López ◽  
Amparo Viramontes-Pintos ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Olfactory Bulb ◽  
Transgenic Mouse ◽  
Tau Protein ◽  
Transgenic Mouse Model ◽  
Model Of Alzheimer’S Disease ◽  
Triple Transgenic Mouse

scholarly journals DNA polymerase β decrement triggers death of olfactory bulb cells and impairs olfaction in a mouse model of Alzheimer's disease

Aging Cell ◽  
2016 ◽  
Vol 16 (1) ◽  
pp. 162-172 ◽  
Author(s):  
Magdalena Misiak ◽  
Rebeca Vergara Greeno ◽  
Beverly A. Baptiste ◽  
Peter Sykora ◽  
Dong Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Olfactory Bulb ◽  
Dna Polymerase ◽  
Dna Polymerase Β ◽  
Model Of Alzheimer’S Disease

Atorvastatin and pitavastatin reduce senile plaques and inflammatory responses in a mouse model of Alzheimer’s disease

2012 ◽  
Vol 34 (6) ◽  
pp. 601-610 ◽  
Author(s):  
Tomoko Kurata ◽  
Kazunori Miyazaki ◽  
Miki Kozuki ◽  
Nobutoshi Morimoto ◽  
Yasuyuki Ohta ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Inflammatory Responses ◽  
Senile Plaques ◽  
Model Of Alzheimer’S Disease

scholarly journals Effect of C-phycocyanin on HDAC3 and miRNA-335 in Alzheimer’s disease

2020 ◽  
Vol 11 (1) ◽  
pp. 161-172
Author(s):  
Zhengyu Li ◽  
Li Gan ◽  
Si Yan ◽  
Yufang Yan ◽  
Wei Huang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Spatial Memory ◽  
Therapeutic Option ◽  
Memory Performance ◽  
Tau Proteins ◽  
Therapeutic Effects ◽  
Epigenetic Factors ◽  
Beneficial Effects ◽  
Ameliorative Effect

AbstractBackground:Amyloid-beta (Aβ) plaque deposits and neurofibrillary tangles containing tau proteins are the key pathognomonic manifestations of Alzheimer’s disease (AD). Lack of holistic drugs for AD has reinvigorated enthusiasm in the natural product-based therapies. In this study, our idea to decipher the beneficial effects of C-phycocyanin (CPC) in the management of AD is buoyed by its multifaceted and holistic therapeutic effects.Methods:We evaluated the effect of CPC treatment on epigenetic factors and inflammatory mediators in a mouse with oligomeric Aβ1-42-induced AD. Besides, the cognitive function was evaluated by the spatial memory performance on a radial arm maze.Results:The results showed cognitive deficit in the mice with AD along with upregulated HDAC3 expression and diminished miRNA-335 and brain-derived neurotrophic factor (BDNF) expressions. In addition, inflammation was provoked (manifested by increased interleukins (IL)-6 and IL-1β) and neuronal apoptosis was accelerated (indicated by increased Bax, caspase-3, and caspase-9 along with decreased Bcl2) in the hippocampus of the mice with AD. Interestingly, CPC treatment in the mice with AD improved spatial memory performance and decreased the perturbations in the epigenetic and inflammatory biofactors.Conclusion:These results underscore that mitigation of inflammation via regulation of epigenetic factors might be the key pathway underlying the ameliorative effect of CPC against the aberrations in AD. Our findings provide the rationale for considering CPC as a viable therapeutic option in the management of AD.

scholarly journals Muramyl dipeptide mediated immunomodulation on monocyte subsets exerts therapeutic effects in a mouse model of Alzheimer’s disease

2020 ◽  
Author(s):  
Adham Fani Malekia ◽  
Giulia Cisbania ◽  
Marie-Michèle Plante ◽  
Paul Préfontaine ◽  
Nataly Laflamme ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Muramyl Dipeptide ◽  
Therapeutic Effects ◽  
Monocyte Subsets ◽  
Expression Levels ◽  
Two Photon Microscopy ◽  
Two Photon ◽  
Model Of Alzheimer’S Disease

Abstract Background Muramyl dipeptide (MDP) is a component derived from minimal peptidoglycan motif from bacteria and it is a ligand for the NOD2 receptor. Peripheral administration of MDP converts Ly6Chigh into Ly6Clow monocytes. Previously we have shown that Ly6Clow monocytes play crucial roles in the pathology of a mouse model of Alzheimer’s disease (AD). However, medications with mild immunomodulatory effects that solely target specific monocyte subsets, without triggering microglial activation are rare. Methods 3-months old APPswe/PS1 transgenic male mice and age-matched C57BL/6J mice were used for high frequency (2-times/week) over 6-months and low frequency (once a week) over a 3-months period of intraperitoneally MDP (10 mg/kg) administrations. Flow cytometry analysis of monocyte subsets in blood, behavioral and post mortem analyses were performed. Two-photon microscopy using APP/PS1/CX3CR1gfp/+ mice were conducted to study vascular Aβ clearance by Ly6Clow monocytes upon MDP administration.Results The treatment improved cognitive declines, increased expression levels of postsynaptic density protein 95 (PSD95) andlow density lipoprotein receptor-related protein 1 (LRP1), which are involved in synaptic plasticity and amyloid beta (Aβ) elimination, respectively. In addition, we found monocyte chemoattractant protein-1(MCP-1) levels significantly increased, whereas intercellular adhesion molecule-1(ICAM-1) significantly decreased and microglial marker (Iba1) did not change in treatment group compared to the control. In parallel, we discovered elevated cyclooxygenase-2 (COX2) expression levels in the treated group, which might be a positive factor for synaptic activity. Following MDP treatment, intravital two-photon microscopy demonstrated that Ly6Clow monocytes are recruited into the brain vasculature in APP but not wild type mice, and they are able to pick up Aβ peptides. Conclusions Our results demonstrate that MDP is beneficial in both the early phase and to some extent later phases of the pathology in the mouse model of AD. These data open the way for potential MDP-based medications for AD.

scholarly journals The Dynamics of β-Amyloid Proteoforms Accumulation in the Brain of a 5xFAD Mouse Model of Alzheimer’s Disease

2021 ◽  
Vol 23 (1) ◽  
pp. 27
Author(s):  
Anna E. Bugrova ◽  
Polina A. Strelnikova ◽  
Maria I. Indeykina ◽  
Alexey S. Kononikhin ◽  
Natalia V. Zakharova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Senile Plaques ◽  
The Elderly ◽  
Mobility Separation ◽  
Model Of Alzheimer’S Disease ◽  
Β Amyloid ◽  
Ion Mobility Separation ◽  
The Brain

Alzheimer’s disease (AD) is the leading cause of dementia among the elderly. Neuropathologically, AD is characterized by the deposition of a 39- to 42-amino acid long β-amyloid (Aβ) peptide in the form of senile plaques. Several post-translational modifications (PTMs) in the N-terminal domain have been shown to increase the aggregation and cytotoxicity of Aβ, and specific Aβ proteoforms (e.g., Aβ with isomerized D7 (isoD7-Aβ)) are abundant in the senile plaques of AD patients. Animal models are indispensable tools for the study of disease pathogenesis, as well as preclinical testing. In the presented work, the accumulation dynamics of Aβ proteoforms in the brain of one of the most widely used amyloid-based mouse models (the 5xFAD line) was monitored. Mass spectrometry (MS) approaches, based on ion mobility separation and the characteristic fragment ion formation, were applied. The results indicated a gradual increase in the Aβ fraction of isoD7-Aβ, starting from approximately 8% at 7 months to approximately 30% by 23 months of age. Other specific PTMs, in particular, pyroglutamylation, deamidation, and oxidation, as well as phosphorylation, were also monitored. The results for mice of different ages demonstrated that the accumulation of Aβ proteoforms correlate with the formation of Aβ deposits. Although the mouse model cannot be a complete analogue of the processes occurring in the human brain in AD, and several of the observed parameters differ significantly from human values supposedly due to the limited lifespan of the model animals, this dynamic study provides evidence on at least one of the possible mechanisms that can trigger amyloidosis in AD, i.e., the hypothesis on the relationship between the accumulation of isoD7-Aβ and the progression of AD-like pathology.

scholarly journals Therapeutic effects of glatiramer acetate and grafted CD115+monocytes in a mouse model of Alzheimer’s disease

Brain ◽  
2015 ◽  
Vol 138 (8) ◽  
pp. 2399-2422 ◽  
Author(s):  
Yosef Koronyo ◽  
Brenda C. Salumbides ◽  
Julia Sheyn ◽  
Lindsey Pelissier ◽  
Songlin Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Glatiramer Acetate ◽  
Therapeutic Effects ◽  
Model Of Alzheimer’S Disease
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