scholarly journals 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)

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.

scholarly journals 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

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.

scholarly journals 418 - Digging signatures modeling anxiety and OCD disorders in very old age and end-of-life Alzheimer’s disease and the effect of social isolation: A translational neuroscience approach in times of coronavirus pandemic (COVID-19)

2020 ◽  
Vol 32 (S1) ◽  
pp. 134-134
Author(s):  
Gimenez-Llort L ◽  
Alveal-Mellado L
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Model ◽  
Social Isolation ◽  
Autism Spectrum ◽  
Wild Mice ◽  
Very Old ◽  
Compulsive Disorder ◽  
Pathological Aging ◽  
Model Of Alzheimer’S Disease

The severity of the current scenarios in this pandemic will leave important psychological traces. In fact, the first clinical reports available already refer to increased incidence of depression and anxiety disorders such as obsessive-compulsive disorder (OCD) and post-traumatic stress disorder. At the translational level, modelling of such neuropsychiatric alterations in animal models relays in neuroethological perspectives since response to fearful situations and traumatic events, critical for survival and adaptation to the environment, are strongly preserved in phylogeny. In the wild, mice dig as a ‘defensive behavior’ which is considered to reflect the anxiety state of animals. In the laboratory, mice dig vigorously in deep bedding to bury food pellets or small objects they may find. Thus this behavior, initially used to screen anxiolytic activity was later proposed to better model meaningless repetitive and perseverative behaviors characteristic of OCD or autism spectrum disorders. In the present work, we have studied the digging 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. We also studied the effects of isolation in this respect, using very old (18 month-old) 3xTg-AD mice that survived to their cage mates, as mortality rates in this animal model are high after 13 months of age. Two digging paradigms, involving different anxiogenic and contextual situations were used to investigate the digging patterns in these very old males with normal and AD-pathological aging, as well as the effects of isolation. The temporal course and intensity of this behavior was found increased in those 3xTg-AD mice that had lost their ‘room partner’ and lived isolated. However, when they were tested under neophobia conditions, incidence of this behavior was smaller and the pattern of digging was disrupted. The results show that this combined paradigm unveils distinct features of digging signatures that can be useful to provide an animal model for these perseverative behaviors and their interplay with anxiety states, which represent an important part of BPSD or can now emerge as a result of the enhancement of obsessive-convulsive behaviors by social-isolation.

scholarly journals Two human metabolites rescue a C. elegans model of Alzheimer’s disease via a cytosolic unfolded protein response

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Priyanka Joshi ◽  
Michele Perni ◽  
Ryan Limbocker ◽  
Benedetta Mannini ◽  
Sam Casford ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Unfolded Protein Response ◽  
Neurodegenerative Disorders ◽  
C Elegans ◽  
Unfolded Protein ◽  
Model Of Alzheimer’S Disease ◽  
Age Related ◽  
Parkinson’S Diseases ◽  
Protein Response

AbstractAge-related changes in cellular metabolism can affect brain homeostasis, creating conditions that are permissive to the onset and progression of neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Although the roles of metabolites have been extensively studied with regard to cellular signaling pathways, their effects on protein aggregation remain relatively unexplored. By computationally analysing the Human Metabolome Database, we identified two endogenous metabolites, carnosine and kynurenic acid, that inhibit the aggregation of the amyloid beta peptide (Aβ) and rescue a C. elegans model of Alzheimer’s disease. We found that these metabolites act by triggering a cytosolic unfolded protein response through the transcription factor HSF-1 and downstream chaperones HSP40/J-proteins DNJ-12 and DNJ-19. These results help rationalise previous observations regarding the possible anti-ageing benefits of these metabolites by providing a mechanism for their action. Taken together, our findings provide a link between metabolite homeostasis and protein homeostasis, which could inspire preventative interventions against neurodegenerative disorders.

Gut Microbiota Alterations and Cognitive Impairment Are Sexually Dissociated in a Transgenic Mice Model of Alzheimer’s Disease

2021 ◽  
pp. 1-20
Author(s):  
Daniel Cuervo-Zanatta ◽  
Jaime Garcia-Mena ◽  
Claudia Perez-Cruz
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Gut Microbiota ◽  
Cognitive Skills ◽  
Amyloid Β ◽  
Short Chain Fatty Acids ◽  
Mice Model ◽  
Model Of Alzheimer’S Disease ◽  
Cognitive Deficiencies

Background: Normal aging is accompanied by cognitive deficiencies, affecting women and men equally. Aging is the main risk factor for Alzheimer’s disease (AD), with women having a higher risk. The higher prevalence of AD in women is associated with the abrupt hormonal decline seen after menopause. However, other factors may be involved in this sex-related cognitive decline. Alterations in gut microbiota (GM) and its bioproducts have been reported in AD subjects and transgenic (Tg) mice, having a direct impact on brain amyloid-β pathology in male (M), but not in female (F) mice. Objective: The aim of this work was to determine GM composition and cognitive dysfunction in M and F wildtype (WT) and Tg mice, in a sex/genotype segregation design. Methods: Anxiety, short term working-memory, spatial learning, and long-term spatial memory were evaluated in 6-month-old WT and Tg male mice. Fecal short chain fatty acids were determined by chromatography, and DNA sequencing and bioinformatic analyses were used to determine GM differences. Results: We observed sex-dependent differences in cognitive skills in WT mice, favoring F mice. However, the cognitive advantage of females was lost in Tg mice. GM composition showed few sex-related differences in WT mice. Contrary, Tg-M mice presented a more severe dysbiosis than Tg-F mice. A decreased abundance of Ruminococcaceae was associated with cognitive deficits in Tg-F mice, while butyrate levels were positively associated with better working- and object recognition-memory in WT-F mice. Conclusion: This report describes a sex-dependent association between GM alterations and cognitive impairment in a mice model of AD.

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
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