Aβ vaccination of a genetic 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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Region- and age-dependent reductions of hippocampal long-term potentiation and NMDA to AMPA ratio in a genetic model of Alzheimer's disease

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2014.07.002 ◽

2015 ◽

Vol 36 (1) ◽

pp. 123-133 ◽

Cited By ~ 18

Author(s):

Alessandro Tozzi ◽

Alessandra Sclip ◽

Michela Tantucci ◽

Antonio de Iure ◽

Veronica Ghiglieri ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Genetic Model ◽

Long Term Potentiation ◽

Model Of Alzheimer’S Disease ◽

Term Potentiation ◽

Age Dependent

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Olfactory Signatures in the Food Finding Test in Mice With Normal and Alzheimer’s Disease-Pathological Aging With Special Concerns on the Effects of Social Isolation

Frontiers in Neuroscience ◽

10.3389/fnins.2021.733984 ◽

2021 ◽

Vol 15 ◽

Author(s):

Daniela Marín-Pardo ◽

Lydia Giménez-Llort

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Social Isolation ◽

Genetic Model ◽

Normal Aging ◽

Male And Female ◽

Pathological Aging ◽

Neurodegenerative Process ◽

Olfactory Loss ◽

Model Of Alzheimer’S Disease

The temporal course and the severity of the involution of sensory systems through aging can be critical since they ensure the ability to perceive and recognize the world. In older people, sensory impairments significantly increase their risk of biological, psychological, and social impoverishment. Besides this, olfactory loss is considered an early biomarker in Alzheimer’s disease (AD) neurodegenerative process. Here we studied olfactory ethograms in middle-aged male and female gold-standard C57BL/6 mice and 3xTg-AD mice, a genetic model of AD that presents cognitive dysfunction and a conspicuous neuropsychiatric-like phenotype. A paradigm involving 1-day food deprivation was used to investigate the ethological patterns shown in the olfactory inspection of a new cage and the sniffing, finding, and eating of hidden food pellets. The sniffing–find–eat temporal patterns were independent of the loss of weight and unveiled (fast) olfactory signatures in Alzheimer’s disease, differing from those (slow progressive) in normal aging. Male 3xTg-AD mice exhibited an early signature than female mice, opposite to animals with normal aging. The sequence of actions was correlated in male and female 3xTg-AD mice in contrast to control mice. Social isolation, naturally occurring in male 3xTg-AD due to the death of cage mates, emphasized their olfactory patterns and disrupted the behavioral correlates. The paradigm provided distinct contextual, sex, and genotype olfactory ethogram signatures useful to investigate olfactory function in normal and AD-pathological aging. Isolation had an impact on enhancing the changes in the olfactory signature here described, for the first time, in the 3xTg-AD model of Alzheimer’s disease.

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417 - Olfactory signatures in models of aging and Alzheimer’s disease and the effect of social isolation: A translational neuroscience approach in times of coronavirus pandemic (COVID-19)

International Psychogeriatrics ◽

10.1017/s1041610220002707 ◽

2020 ◽

Vol 32 (S1) ◽

pp. 133-133

Author(s):

Daniela Marín-Pardo ◽

Lydia Gimenez-Llort

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Social Isolation ◽

Viral Infections ◽

Genetic Model ◽

Normal Aging ◽

Mice Model ◽

Pathological Aging ◽

Model Of Alzheimer’S Disease ◽

Parkinson’S Diseases

Sensory systems ensure the ability to perceive and recognize the world. Therefore, the temporal course and the severity of their involution through the aging process can be critical. In the elderly, sensory impairments significantly increase their risk of biological, psychological and social impoverishment. Olfactory loss, known to happen in bacterial and viral infections and considered an early biomarker in Alzheimer’s and Parkinson’s diseases neurodegenerative processes, has been reported also as an early indicator of current infection by SARS-CoV-2. At the translational level, in the present work, we have studied olfactory ethograms in normal and advanced AD-related pathological aging using wildtype and the 3xTg-AD mice, a genetic model of Alzheimer’s disease that presents AD-cognitive dysfunction but also a conspicuous BPSD-like phenotype. An olfactory paradigm, involving the equivalent to one day food deprivation, was used to investigate in middle-aged males and females with normal and AD-pathological aging the ethological patterns shown in the olfactory inspection of a new cage with beddings and the posterior detection, finding and consumption of food pellets hidden in this new anxiogenic environment. Males with normal and pathological aging were equally delayed in their first contact with food pellets, while in female sex this latency was dependent on the genotype (longer in 3xTg-AD mice, shorter in those with normal aging). Once the animals had inspected the arena, the latencies to smell, find and eat the food pellets were found progressively increased in males with normal aging, but consecutively developed in 3xTg-AD mice. In contrast, both groups of females exhibited longer delays as compared to males, and the temporal pattern of their ethogram to smell-find-eat the food was faster. In 3xTg-AD males, social isolation (naturally occurring due to death of counterparts) emphasized these olfactory patterns, which were independent of the punctual loss of weight of this paradigm. The results show that this paradigm provides distinct contextual, sex and genotype olfactory ethogram signatures useful to investigate olfactory function in normal and AD-pathological aging. Also, that isolation has an impact enhancing the changes in the olfactory signature here described, for the first time, in the 3xTg-AD mice model of Alzheimer’s disease.

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