scholarly journals EFAD transgenic mice as a humanAPOErelevant preclinical model of Alzheimer’s disease

2017 ◽  
Vol 58 (9) ◽  
pp. 1733-1755 ◽  
Author(s):  
Leon M. Tai ◽  
Deebika Balu ◽  
Evangelina Avila-Munoz ◽  
Laila Abdullah ◽  
Riya Thomas ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Preclinical Model ◽  
Model Of Alzheimer’S Disease

scholarly journals Improved Bioavailability of Montelukast through a Novel Oral Mucoadhesive Film in Humans and Mice

Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 12
Author(s):  
Johanna Michael ◽  
Diana Bessa de Sousa ◽  
Justin Conway ◽  
Erick Gonzalez-Labrada ◽  
Rodolphe Obeid ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Neurodegenerative Diseases ◽  
Significant Proportion ◽  
Preclinical Model ◽  
Dependent Manner ◽  
Promising Alternative ◽  
Model Of Alzheimer’S Disease ◽  
Acute And Chronic Exposure

The leukotriene receptor antagonist Montelukast (MTK) is an approved medication for the treatment of asthma and allergic rhinitis. The existing marketed tablet forms of MTK exhibit inconsistent uptake and bioavailability, which partially explains the presence of a significant proportion of MTK low- and non-responders in the population. Besides that, tablets are suboptimal formulations for patients suffering from dysphagia, for example, seen in patients with neurodegenerative diseases such as Alzheimer’s disease, a disease with increasing interest in repurposing of MTK. This, and the need for an improved bioavailability, triggered us to reformulate MTK. Our aim was to develop a mucoadhesive MTK film with good safety and improved pharmacological features, i.e., an improved bioavailability profile in humans as well as in a mouse model of Alzheimer’s disease. We tested dissolution of the MTK mucoadhesive film and assessed pharmacoexposure and kinetics after acute and chronic oral application in mice. Furthermore, we performed a Phase I analysis in humans, which included a comparison with the marketed tablet form as well as a quantitative analysis of the MTK levels in the cerebrospinal fluid. The novel MTK film demonstrated significantly improved bioavailability compared to the marketed tablet in the clinical Phase 1a study. Furthermore, there were measurable amounts of MTK present in the cerebrospinal fluid (CSF). In mice, MTK was detected in serum and CSF after acute and chronic exposure in a dose-dependent manner. The mucoadhesive film of MTK represents a promising alternative for the tablet delivery. The oral film might lower the non-responder rate in patients with asthma and might be an interesting product for repurposing of MTK in other diseases. As we demonstrate Blood-Brain-Barrier (BBB) penetrance in a preclinical model, as well as in a clinical study, the oral film of MTK might find its use as a therapeutic for acute and chronic neurodegenerative diseases such as dementias and stroke.

P1-031: Age-related cerebral changes of brain-derived neurotrophic factor in a model of Alzheimer's disease in APP23 transgenic mice

2006 ◽  
Vol 2 ◽  
pp. S103-S103
Author(s):  
Olaf Schulte-Herbrüggen ◽  
Uwe Deicke ◽  
Uwe Otten ◽  
Dorothee Abramowski ◽  
Matthias Staufenbiel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Neurotrophic Factor ◽  
Brain Derived Neurotrophic Factor ◽  
Model Of Alzheimer’S Disease ◽  
Age Related

Consumption of fig fruits grown in Oman can improve memory, anxiety, and learning skills in a transgenic mice model of Alzheimer's disease

2016 ◽  
Vol 19 (10) ◽  
pp. 475-483 ◽  
Author(s):  
Selvaraju Subash ◽  
Musthafa Mohamed Essa ◽  
Nady Braidy ◽  
Ahood Al-Jabri ◽  
Ragini Vaishnav ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Mice Model ◽  
Learning Skills ◽  
Model Of Alzheimer’S Disease

Aspects of spatial memory and behavioral disinhibition in Tg2576 transgenic mice as a model of Alzheimer’s disease

2005 ◽  
Vol 156 (2) ◽  
pp. 225-232 ◽  
Author(s):  
Elisa Ognibene ◽  
Silvia Middei ◽  
Stefania Daniele ◽  
Walter Adriani ◽  
Orlando Ghirardi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Spatial Memory ◽  
Behavioral Disinhibition ◽  
Model Of Alzheimer’S Disease

Long-term (15 mo) dietary supplementation with pomegranates from Oman attenuates cognitive and behavioral deficits in a transgenic mice model of Alzheimer's disease

Nutrition ◽  
2015 ◽  
Vol 31 (1) ◽  
pp. 223-229 ◽  
Author(s):  
Selvaraju Subash ◽  
Nady Braidy ◽  
Musthafa Mohamed Essa ◽  
Al-Buraiki Zayana ◽  
Vaishnav Ragini ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Dietary Supplementation ◽  
Mice Model ◽  
Behavioral Deficits ◽  
Model Of Alzheimer’S Disease

scholarly journals Telomere length and oxidative stress variations in a murine model of Alzheimer’s disease progression

2019 ◽  
Author(s):  
Katia Martínez-González ◽  
Azul Islas-Hernández ◽  
José Darío Martínez-Ezquerro ◽  
Federico Bermúdez-Rattoni ◽  
Paola Garcia-delaTorre
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Telomere Length ◽  
Brain Tissue ◽  
Murine Model ◽  
Blood Cells ◽  
Model Of Alzheimer’S Disease ◽  
And Oxidative Stress

AbstractAlzheimer’s Disease (AD) is the most common cause of dementia and aging is its major risk factor. Changes in telomere length have been associated with aging and some degenerative diseases. Our aim was to explore some of the molecular changes caused by the progression of AD in a transgenic murine model (3xTg-AD; B6; 129-Psen1 <tm1Mpm> Tg (APPSwe, tauP301L) 1Lfa). Telomere length was assessed by qPCR in both brain tissue and peripheral blood cells and compared between three age groups: 5, 9, and 13 months. In addition, a possible effect of oxidative stress on telomere length and AD progression was explored. Shorter telomeres were found in blood cells of older transgenic mice compared to younger and wild type mice but no changes in telomere length in the hippocampus. An increase in oxidative stress with age was found for all strains but no correlation was found between oxidative stress and shorter telomere length for transgenic mice. Telomere length and oxidative stress are affected by AD progression in the 3xTg-AD murine model. Changes in blood cells are more noticeable than changes in brain tissue, suggesting that systemic changes can be detected early in the disease in this murine model.

scholarly journals Adrenergic mechanisms of myocardium contractility regulation in genetic model of Alzheimer’s disease

2015 ◽  
Vol 96 (1) ◽  
pp. 50-55 ◽  
Author(s):  
A V Leushina ◽  
L F Nurullin ◽  
E O Petukhova ◽  
A L Zefirov ◽  
M A Mukhamedyarov
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Adrenergic Receptors ◽  
Myocardial Contractility ◽  
Genetic Model ◽  
Immunofluorescent Staining ◽  
Wild Type ◽  
Adrenergic Mechanisms ◽  
Model Of Alzheimer’S Disease

Aim. Study is aimed to investigate contractility impairments and receptor mechanisms of adrenergic regulation of myocardium inotropic function in Alzheimer’s disease model on transgenic mice.Methods. Experiments were performed on isolated preparations of atria and ventricles myocardium of mice. Transgenic mice of B6C3-Tg(APP695)85Dbo Tg(PSENI)85Dbo genotype were used as animal model of Alzheimer’s disease. Contractile responses of myocardium were registered by conventional myographic technique in isometric conditions. To evaluate the expression of adrenergic receptors, immunofluorescence staining of myocardium with specific antibodies was performed.Results. Transgenic mice showed not only a decreased effect of norepinephrine on myocardium inotropic function but also the inversion of the effect of norepinephrine - the use of 10-5-10-4 M of norepinephrine decreased myocardium inotropic function. Immunofluorescent staining showed decrease of expression of β1- and especially β2-adrenergic receptors ventricular myocardium of transgenic mice comparing to wild type mice. Adrenergic deregulation was registered in ventricles, but not in atria. The features of adrenergic regulatory mechanisms of myocardial contractility in transgenic APP/PS1 mice aged 8-10 months are specific, although somewhat similar to wild type mice aged 8-10 months, and are evidently due to Alzheimer’s disease. The inversion of norepinephrine inotropic effect (from positive to negative) may be explained by switching the intracellular cascade pathway of β2-adrenergic receptors effects to another type of G-protein.Conclusion. The results indicate that peripheral adrenergic mechanisms of myocardial contractility regulation are impaired in studied transgenic mice model of Alzheimer’s disease. Obtained data widen our understanding of Alzheimer’s disease pathogenesis, as well as our conception of relations between cardiovascular diseases and neurodegeneration.

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