scholarly journals Insulin gene expression and functional activity of insulin signaling pathway in Alzheimer's disease

2021 ◽  
Vol 6 (4) ◽  
pp. 8-21
Author(s):  
Y. V. Gorina ◽  
E. D. Khilazheva ◽  
Yu. K. Komleva ◽  
O. L. Lopatina ◽  
A. B. Salmina
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Insulin Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Adapter Protein ◽  
Brain Areas ◽  
Model Of Alzheimer’S Disease ◽  
Β Amyloid

Aim. To study the insulin (INS) gene expression, insulin and lactate levels, expression of Fe65 adapter protein, and level of oxidative DNA damage marker γH2AX in different brain areas in the experimental model of Alzheimer's disease.Materials and Methods. Male, 4-month-old C57BL/6 mice received either intrahippocampal injection of β-amyloid (C57BL/6 + Aβ 1-42) or phosphate-buffered saline (C57BL/6 + PBS). Insulin (INS) gene expression in the hippocampus and amygdala was assessed by means of reverse transcription-polymerase chain reaction. Levels of lactate and insulin in different brain areas were measured by enzyme-linked immunosorbent assay. Expression of Fe65 adapter protein and γH2AX in the hippocampus was studied by immunofluorescence staining followed by confocal microscopy.Results. We found an overexpression of the INS gene in the hippocampus and amygdala, an increase in lactate level in the hippocampus, and slightly increased insulin level in the amygdala of mice with Alzheimer's disease as compared with the control group. Neurodegeneration was accompanied by an elevated endothelial expression of Fe65 adapter protein (p= 0.04) and γH2AX in hippocampal neurons (p = 0.04).Conclusion. Alzheimer's disease neurodegeneration is accompanied by a disrupted insulin signaling and impaired glucose metabolism in the hippocampus and amygdala. This further leads to a neuronal accumulation of γH2AX and impaired amyloid precursor protein proteolysis because of insulin inability to inhibit its interaction with the Fe65 adapter protein and to prevent formation and deposition of β-amyloid.

Alzheimer’s Disease: Erythrocyte 2,3-diphosphoglycerate Content and Circulating Erythropoietin

2019 ◽  
Vol 16 (9) ◽  
pp. 834-835
Author(s):  
Petter Järemo ◽  
Alenka Jejcic ◽  
Vesna Jelic ◽  
Tasmin Shahnaz ◽  
Homira Behbahani ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cell Damage ◽  
Control Group ◽  
Red Cell ◽  
Oxygen Release ◽  
Regulatory Pathways ◽  
Β Amyloid ◽  
2,3 Dpg

Background: Alzheimer’s Disease (AD) features the accumulation of β-amyloid in erythrocytes. The subsequent red cell damage may well affect their oxygen-carrying capabilities. 2,3- diphosphoglycerate (2,3-DPG) binds to the hemoglobin thereby promoting oxygen release. It is theorized that 2,3-DPG is reduced in AD and that the resulting hypoxia triggers erythropoietin (EPO) release. Methods & Objective: To explore this theory, we analyzed red cell 2,3-DPG content and EPO in AD, mild cognitive impairment, and the control group, subjective cognitive impairment. Results: We studied (i) 2,3-DPG in red cells, and (ii) circulating EPO in AD, and both markers were unaffected by dementia. Disturbances of these oxygen-regulatory pathways do not appear to participate in brain hypoxia in AD.

scholarly journals P3-270: CHF5074 reduces brain β-amyloid burden and hyperphosphorylated tau in a mouse model of Alzheimer's disease

2009 ◽  
Vol 5 (4S_Part_14) ◽  
pp. P422-P422
Author(s):  
M. Pizzi ◽  
A. Lanzillotta ◽  
B.P. Imbimbo ◽  
B. Hutter-Paier ◽  
G. Villetti ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Hyperphosphorylated Tau ◽  
Amyloid Burden ◽  
Model Of Alzheimer’S Disease ◽  
Β Amyloid

The β-Amyloid Model of Alzheimer’s Disease

1997 ◽  
pp. 73-90 ◽  
Author(s):  
Carl W. Cotman ◽  
David H. Cribbs ◽  
Aileen J. Anderson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Model Of Alzheimer’S Disease ◽  
Β Amyloid

scholarly journals Gestational Stress Augments Postpartum β-Amyloid Pathology and Cognitive Decline in a Mouse Model of Alzheimer’s Disease

2018 ◽  
Vol 29 (9) ◽  
pp. 3712-3724 ◽  
Author(s):  
Zahra Jafari ◽  
Jogender Mehla ◽  
Bryan E Kolb ◽  
Majid H Mohajerani
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Cognitive Decline ◽  
Noise Exposure ◽  
Amyloid Β ◽  
Control Group ◽  
Plaque Size ◽  
Model Of Alzheimer’S Disease ◽  
Gestational Stress

Abstract Besides well-known risk factors for Alzheimer’s disease (AD), stress, and in particular noise stress (NS), is a lifestyle risk factor common today. It is known that females are at a significantly greater risk of developing AD than males, and given that stress is a common adversity in females during pregnancy, we hypothesized that gestational noise exposure could exacerbate the postpartum development of the AD-like neuropathological changes during the life span. Pregnant APPNL-G-F/NL-G-F mice were randomly assigned to either the stress condition or control group. The stress group was exposed to the NS on gestational days 12–16, which resulted in a markedly higher hypothalamic–pituitary–adrenal (HPA) axis responsivity during the postpartum stage. Higher amyloid-β (Aβ) deposition and larger Aβ plaque size in the olfactory area were the early onset impacts of the gestational stress (GS) seen at the age of 4 months. This pattern of increased Aβ aggregation and larger plaque size were observed in various brain areas involved in both AD and stress regulation, especially in limbic structures, at the age of 6 months. The GS also produced anxiety-like behavior, deficits in learning and memory, and impaired motor coordination. The findings suggest that environmental stresses during pregnancy pose a potential risk factor in accelerating postpartum cognitive decline and AD-like neuropathological changes in the dams (mothers) later in life.

scholarly journals Microglial and Astrocyte priming in the APP/PS1 model of Alzheimer’s Disease: increased vulnerability to acute inflammation and cognitive deficits

2018 ◽  
Author(s):  
Ana Belen Lopez-Rodriguez ◽  
Edel Hennessy ◽  
Carol Murray ◽  
Anouchka Lewis ◽  
Niamh de Barra ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Deficits ◽  
Inflammasome Activation ◽  
Nuclear Localisation ◽  
Amyloid Pathology ◽  
Model Of Alzheimer’S Disease ◽  
Nlrp3 Inflammasome Activation ◽  
Β Amyloid ◽  
Secondary Stimulation

AbstractAlzheimer’s disease (AD) causes devastating cognitive decline and has no disease-modifying therapies. Neuroinflammation is a significant contributor to disease progression but its precise contribution remains unclear. An emerging literature indicates that secondary inflammatory insults including acute trauma and infection alter the trajectory of chronic neurodegenerative diseases and the roles of microglia and astrocytes require elucidation. The current study, using the APP/PS1 mouse model of AD, demonstrates that microglia are primed by β-amyloid pathology to induce exaggerated IL-1β responses to acute stimulation with LPS or IL-1β. Despite disease-associated NLRP3 inflammasome activation, evidenced by ASC speck formation, APP/PS1 microglial cells show neither IL-1β induction nor NFκB p65 nuclear localisation. Upon secondary stimulation with LPS or IL-1β, NFκB-p65 nuclear localisation and exaggerated pro-IL-1 induction occur. Microglial priming was also unmasked by secondary stimulation with systemic LPS leading to significant cognitive impairment in APP/PS1 mice compared to WT LPS-treated mice. Astrocytes have also recently emerged as displaying significant phenotypic heterogeneity. Here, by-passing microglial priming, and acutely challenging mice with intra-hippocampal IL-1β we demonstrate that astrocytes proximal to Aβ-plaques are also primed to produce exaggerated CCL2, CXCL1 and CXCL10 responses. Many astrocytosis-associated genes in APP/PS1 mice share these exaggerated responses to IL-1β, while others are equally induced in both strains. Collectively the data show that the amyloid-laden brain shows multiple vulnerabilities to secondary inflammatory challenge: both microglia and astrocytes are primed to produce exaggerated secondary inflammation and systemic LPS is sufficient to cause cognitive impairments relevant to delirium, selectively in animals with prior amyloid pathology.

scholarly journals Studying the Relationship of Intermittent Fasting and β-Amyloid in Animal Model of Alzheimer’s Disease: A Scoping Review

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3215
Author(s):  
Muhammad Luqman Nasaruddin ◽  
Syarifah Aisyah Syed Abd Halim ◽  
Mohd Amir Kamaruzzaman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Dietary Habits ◽  
Longitudinal Research ◽  
Intermittent Fasting ◽  
Restricted Feeding ◽  
Model Of Alzheimer’S Disease ◽  
Alternate Day Fasting ◽  
Β Amyloid

We examined the evidence for intermittent fasting (IF) as a preventative tool to influence β-amyloid in animal models of Alzheimer’s disease (AD). A Scopus, Ovid, PubMed, and Web of Science (WoS), search yielded 29 results using the keywords “amyloid beta”, “intermittent fasting”, “intermittent caloric restriction”, “alternate day fasting”, “modified alternate-day fasting”, “time-restricted feeding”, “Ramadan fast”, “intermittent calori* restriction”, “intermittent restrictive diet”, and “Alzheimer*”. Five research articles addressed directly the effects of intermittent fasting on β-amyloid levels in animal models of AD: alternate day fasting (ADF) and time-restricted feeding (TRF) methods were incorporated in these studies. The study designs were found to be heterogeneous. Variations in the levels of β-amyloid peptides or plaque in either the hippocampus, cortical areas, or both in animals following dietary intervention were observed as compared to the ad libitum group. Non-significant changes were observed in three studies, while two studies interestingly demonstrated amelioration and reduction in β-amyloid levels. Given the conflicting results obtained from this study, significant care has to be taken into consideration before the protocol can be applied as a preventative approach to treat Alzheimer’s disease. Longitudinal research is warranted to fully grasp how dietary habits can help alleviate the disease either through upstream or downstream of AD pathology.

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