scholarly journals Early Spatial Memory Impairment in a Double Transgenic Model of Alzheimer’s Disease TgF-344 AD

2021 ◽  
Vol 11 (10) ◽  
pp. 1300
Author(s):  
Stephanie L. Proskauer Proskauer Pena ◽  
Konstantinos Mallouppas ◽  
Andre M. G. Oliveira ◽  
Frantisek Zitricky ◽  
Athira Nataraj ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Spatial Orientation ◽  
Cognitive Abilities ◽  
Disease Model ◽  
Transgenic Animals ◽  
Hippocampal Damage ◽  
Avoidance Task ◽  
Male And Female ◽  
Model Of Alzheimer’S Disease

Before the course of Alzheimer’s disease fully manifests itself and largely impairs a patient’s cognitive abilities, its progression has already lasted for a considerable time without being noticed. In this project, we mapped the development of spatial orientation impairment in an active place avoidance task—a highly sensitive test for mild hippocampal damage. We tested vision, anxiety and spatial orientation performance at four age levels of 4, 6, 9, and 12 months across male and female TgF-344 AD rats carrying human genes for presenilin-1 and amyloid precursor protein. We found a progressive deterioration of spatial navigation in transgenic animals, beginning already at the age of 4 months, that fully developed at 6 months of age across both male and female groups, compared to their age-matched controls. In addition, we described the gradual vision impairment that was accentuated in females at the age of 12 months. These results indicate a rather early onset of cognitive impairment in the TgF-344 AD Alzheimer’s disease model, starting earlier than shown to date, and preceding the reported development of amyloid plaques.

Neuroprotective Role of Diosgenin, A NGF Stimulator, Against Aβ (1–42) Induced Neurotoxicity in Animal Model of Alzheimer’s Disease

2021 ◽  
Author(s):  
Swati Som ◽  
Justin Antony ◽  
Palanisamy Dhanabal ◽  
Ponnusankar Sivasankaran
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Molecular Mechanisms ◽  
Protective Action ◽  
Amyloid Β ◽  
Spatial Learning And Memory ◽  
Avoidance Task ◽  
Model Of Alzheimer’S Disease

Abstract Diosgenin is a neurosteroid derived from the plants and has been previously reported for its numerous health beneficial properties, such as anti-arrhythmic, hypolipidemic, and antiproliferative effects. Although several studies conducted earlier suggested cognition enhancement actions of diosgenin against neurodegenerative disorders, but the molecular mechanisms underlying are not clearly understood. In the present study, we investigated the neuroprotective effect of diosgenin in the wistar rats that received an intracerebroventricular injection of Amyloid-β (1–42) peptides, representing a rodent model of Alzheimer’s disease (AD). Animals were treated with 100 and 200 mg/kg/p.o of diosgenin for 28 days, followed by Amyloid-β (1–42) peptides infusion. Animals were assessed for the spatial learning and memory by using radial arm maze and passive avoidance task. Subsequently, animals were euthanized and brains were collected for biochemical estimations and histopathological studies. Our results revealed that, diosgenin administration dose dependently improved the spatial learning and memory and protected the animals from Amyloid-β (1–42) peptides induced disrupted cognitive functions. Further, biochemical analysis showed that diosgenin successfully attenuated Amyloid-β (1–42) mediated plaque load, oxidative stress, neuroinflammation and elevated acetylcholinesterase activity. In addition, histopathological evaluation also supported neuroprotective effects of diosgenin in hippocampus of rat brain when assessed using hematoxylin-eosin and Cresyl Violet staining. Thus, the aforementioned effects suggested protective action of diosgenin against Aβ (1–42) induced neuronal damage and thereby can serve as a potential therapeutic candidate for AD.

scholarly journals Bupropion and Citalopram in the APP23 Mouse Model of Alzheimer's Disease: A Study in a Dry-Land Maze

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Katharina L. Neumeister ◽  
Matthias W. Riepe
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Spatial Learning ◽  
Transgenic Animals ◽  
Transgenic Animal ◽  
Wild Type ◽  
Dry Land ◽  
Psychomotor Activity ◽  
Model Of Alzheimer’S Disease ◽  
Resting Time

Background. Incipient Alzheimer's disease is often disguised as depressive disorder. Over the course of AD, depressive symptoms are even more frequent. Hence, treatment with antidepressants is common in AD. It was the goal of the present study to assess whether two common antidepressants with different mechanisms of action affect spatial learning in a transgenic animal model of Alzheimer's disease.Methods. We assessed spatial memory of male wild-type and B6C3-Tg(APPswe,PSEN1dE9)85Dbo (APP23) transgenic animals in a complex dry-land maze. Animals were treated with citalopram (10 mg/kg) and bupropion (20 mg/kg).Results. Moving and resting time until finding the goal zone decreased in 4.5-month-old sham-treated wild-type animals and, to a lesser extent, in APP23 animals. Compared with sham-treated APP23 animals, treatment with bupropion reduced resting time and increased speed. On treatment with citalopram, moving and resting time were unchanged but speed decreased. Length of the path to the goal zone did not change on either bupropion or citalopram.Conclusion. Bupropion increases psychomotor activity in APP23 transgenic animals, while citalopram slightly reduces psychomotor activity. Spatial learning per se is unaffected by treatment with either bupropion or citalopram.

scholarly journals The effect of miR-101 on the memory of rats with a model of Alzheimer’s disease

2020 ◽  
Vol 11 (3) ◽  
pp. 354-359
Author(s):  
O. G. Berchenko ◽  
N. O. Levicheva ◽  
D. O. Bevzyuk ◽  
V. V. Sokolik
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Working Memory ◽  
Spatial Memory ◽  
Spatial Orientation ◽  
Emotional Memory ◽  
Amyloid Peptide ◽  
Adaptive Behaviour ◽  
Research Activity ◽  
Model Of Alzheimer’S Disease

Memory impairment is a hallmark of Alzheimer’s disease. The clinical diagnosis of the disease is made in the later stages of its development, when specific therapy of the disease is not always effective. Therefore, the detection of early behavioral manifestations of memory disorders in the development of the disease will allow the use of preventive therapy aimed at stopping the death of neurons in brain structures. A neuroethological study of working, spatial, and emotional memory was performed in rats 15–16 months of age with a model of early manifestations of Alzheimer’s disease induced by stereotactic administration of β-amyloid peptide 40 aggregates into the hippocampus. Changes in the neuroethological components of working and spatial memory have been identified. Testing of working memory showed a violation in rats of recognizing the shape of identical objects, reducing experimental activity to unfamiliar objects and their differentiation. Spatial orientation disorders have been identified in the Barnes labyrinth. Emotional memory research has shown the preservation of innate forms of protective adaptive behaviour. At the same time, vegetative indicators reflected an increase in emotional tension. Intranasal administration of liposomal miRNA miR-101 involved in liposomes to rats with a model of early manifestations of Alzheimer’s disease improved neuroethological parameters of working and spatial memory. Restoration of the level of research activity and differentiation of familiar and unfamiliar objects in the testing of working memory in rats has been established. Spatial memory in Barnes labyrinth testing was improved by reproducing spatial orientation skills and relieving emotional stress. Thus, the intranasal use of miR-101 in Alzheimer’s disease is a promising approach to prevent the development of amyloidosis and preserve memory in the early manifestations of Alz-heimer’s disease.

scholarly journals Enduring glucocorticoid-evoked exacerbation of synaptic plasticity disruption in male rats modelling early Alzheimer’s disease amyloidosis

2021 ◽  
Author(s):  
Yingjie Qi ◽  
Igor Klyubin ◽  
Tomas Ondrejcak ◽  
Neng-Wei Hu ◽  
Michael J. Rowan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Transgenic Animals ◽  
Long Term Potentiation ◽  
Male Rats ◽  
Model Of Alzheimer’S Disease ◽  
Term Potentiation ◽  
Early Alzheimer’S Disease

AbstractSynaptic dysfunction is a likely proximate cause of subtle cognitive impairment in early Alzheimer’s disease. Soluble oligomers are the most synaptotoxic forms of amyloid ß-protein (Aß) and mediate synaptic plasticity disruption in Alzheimer’s disease amyloidosis. Because the presence and extent of cortisol excess in prodromal Alzheimer’s disease predicts the onset of cognitive symptoms we hypothesised that corticosteroids would exacerbate the inhibition of hippocampal synaptic long-term potentiation in a rat model of Alzheimer’s disease amyloidosis. In a longitudinal experimental design using freely behaving pre-plaque McGill-R-Thy1-APP male rats, three injections of corticosterone or the glucocorticoid methylprednisolone profoundly disrupted long-term potentiation induced by strong conditioning stimulation for at least 2 months. The same treatments had a transient or no detectible detrimental effect on synaptic plasticity in wild-type littermates. Moreover, corticosterone-mediated cognitive dysfunction, as assessed in a novel object recognition test, was more persistent in the transgenic animals. Evidence for the involvement of pro-inflammatory mechanisms was provided by the ability of the selective the NOD-leucine rich repeat and pyrin containing protein 3 (NLRP3) inflammasome inhibitor Mcc950 to reverse the synaptic plasticity deficit in corticosterone-treated transgenic animals. The marked prolongation of the synaptic plasticity disrupting effects of brief corticosteroid excess substantiates a causal role for hypothalamic-pituitary-adrenal axis dysregulation in early Alzheimer’s disease.

scholarly journals A General Approach to Convert Hemicyanine Dyes into Highly Optimized Photoacoustic Scaffolds for Analyte Sensing

2021 ◽  
Author(s):  
Sarah Garder ◽  
Catharine Brady ◽  
Cameron Keeton ◽  
Anuj K Yadav ◽  
Sharath C Mallojjala ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Photoacoustic Imaging ◽  
Disease Model ◽  
Photoacoustic Signal ◽  
Model Of Alzheimer’S Disease ◽  
5Xfad Mice ◽  
The Impact

<p>In the context of deep-tissue disease biomarker detection and analyte sensing of biologically relevant species, the impact of photoacoustic imaging has been profound. However, most photoacoustic imaging agents to date are based on the repurposing of existing fluorescent dye platforms that exhibit non-optimal properties for photoacoustic applications (e.g., high fluorescence quantum yield). Herein, we introduce two effective modifications to the hemicyanine dye to afford PA-HD, a new dye scaffold optimized for photoacoustic probe development. We observed a significant increase in the photoacoustic output, representing an increase in sensitivity of 4.8-fold and a red-shift of the λ<sub>abs</sub> from 690 nm to 745 nm to enable ratiometric imaging. Moreover, to demonstrate the generalizability and utility of our remodeling efforts, we developed three probes using common analyte-responsive triggers for beta-galactosidase activity (PA-HD-Gal), nitroreductase activity (PA-HD-NTR), and hydrogen peroxide (PA-HD-H<sub>2</sub>O<sub>2</sub>). The performance of each probe (responsiveness, selectivity) was evaluated <i>in vitro</i> and <i>in cellulo</i>. To showcase the enhance properties afforded by PA-HD for <i>in vivo</i> photoacoustic imaging, we employed an Alzheimer’s disease model to detect H<sub>2</sub>O<sub>2</sub>. In particular, the photoacoustic signal at 735 nm in the brains of 5xFAD mice (a murine model of Alzheimer’s disease) increased by 1.72 ± 0.20-fold relative to background indicating the presence of oxidative stress, whereas the change in wildtype mice was negligible (1.02 ± 0.14). These results were confirmed via ratiometric calibration which was not possible using the parent HD platform.</p>

scholarly journals Effects of Magnesium Orotate, Benfotiamine and a Combination of Vitamins on Mitochondrial and Cholinergic Function in the TgF344-AD Rat Model of Alzheimer’s Disease

2021 ◽  
Vol 14 (12) ◽  
pp. 1218
Author(s):  
Christian Viel ◽  
Adrian T. Brandtner ◽  
Alexander Weißhaar ◽  
Alina Lehto ◽  
Marius Fuchs ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Animals ◽  
Wild Type ◽  
Transgenic Rats ◽  
Cholinergic Dysfunction ◽  
Model Of Alzheimer’S Disease ◽  
Lactate And Pyruvate ◽  
Magnesium Orotate ◽  
F344 Rats

Glucose hypometabolism, mitochondrial dysfunction, and cholinergic deficits have been reported in early stages of Alzheimer’s disease (AD). Here, we examine these parameters in TgF344-AD rats, an Alzheimer model that carries amyloid precursor protein and presenilin-1 mutations, and of wild type F344 rats. In mitochondria isolated from rat hippocampi, we found reductions of complex I and oxidative phosphorylation in transgenic rats. Further impairments, also of complex II, were observed in aged (wild-type and transgenic) rats. Treatment with a “cocktail” containing magnesium orotate, benfotiamine, folic acid, cyanocobalamin, and cholecalciferol did not affect mitochondrial activities in wild-type rats but restored diminished activities in transgenic rats to wild-type levels. Glucose, lactate, and pyruvate levels were unchanged by age, genetic background, or treatment. Using microdialysis, we also investigated extracellular concentrations of acetylcholine that were strongly reduced in transgenic animals. Again, ACh levels in wild-type rats did not change upon treatment with nutrients, whereas the cocktail increased hippocampal acetylcholine levels under physiological stimulation. We conclude that TgF344-AD rats display a distinct mitochondrial and cholinergic dysfunction not unlike the findings in patients suffering from AD. This dysfunction can be partially corrected by the application of the “cocktail” which is particularly active in aged rats. We suggest that the TgF344-AD rat is a promising model to further investigate mitochondrial and cholinergic dysfunction and potential treatment approaches for AD.

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 A General Approach to Convert Hemicyanine Dyes into Highly Optimized Photoacoustic Scaffolds for Analyte Sensing

2021 ◽  
Author(s):  
Sarah Garder ◽  
Catharine Brady ◽  
Cameron Keeton ◽  
Anuj K Yadav ◽  
Sharath C Mallojjala ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Photoacoustic Imaging ◽  
Disease Model ◽  
Photoacoustic Signal ◽  
Model Of Alzheimer’S Disease ◽  
5Xfad Mice ◽  
The Impact

<p>In the context of deep-tissue disease biomarker detection and analyte sensing of biologically relevant species, the impact of photoacoustic imaging has been profound. However, most photoacoustic imaging agents to date are based on the repurposing of existing fluorescent dye platforms that exhibit non-optimal properties for photoacoustic applications (e.g., high fluorescence quantum yield). Herein, we introduce two effective modifications to the hemicyanine dye to afford PA-HD, a new dye scaffold optimized for photoacoustic probe development. We observed a significant increase in the photoacoustic output, representing an increase in sensitivity of 4.8-fold and a red-shift of the λ<sub>abs</sub> from 690 nm to 745 nm to enable ratiometric imaging. Moreover, to demonstrate the generalizability and utility of our remodeling efforts, we developed three probes using common analyte-responsive triggers for beta-galactosidase activity (PA-HD-Gal), nitroreductase activity (PA-HD-NTR), and hydrogen peroxide (PA-HD-H<sub>2</sub>O<sub>2</sub>). The performance of each probe (responsiveness, selectivity) was evaluated <i>in vitro</i> and <i>in cellulo</i>. To showcase the enhance properties afforded by PA-HD for <i>in vivo</i> photoacoustic imaging, we employed an Alzheimer’s disease model to detect H<sub>2</sub>O<sub>2</sub>. In particular, the photoacoustic signal at 735 nm in the brains of 5xFAD mice (a murine model of Alzheimer’s disease) increased by 1.72 ± 0.20-fold relative to background indicating the presence of oxidative stress, whereas the change in wildtype mice was negligible (1.02 ± 0.14). These results were confirmed via ratiometric calibration which was not possible using the parent HD platform.</p>

scholarly journals The effect of PN-1, a Traditional Chinese Prescription, on the Learning and Memory in a Transgenic Mouse Model of Alzheimer’s Disease

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Zhi-Gang Yao ◽  
Ling Zhang ◽  
Liang Liang ◽  
Yu Liu ◽  
Ya-Jun Yang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Learning And Memory ◽  
Protein A ◽  
Transgenic Animals ◽  
Plaque Burden ◽  
Intragastric Administration ◽  
Amyloid Beta Protein ◽  
Promising Alternative ◽  
Model Of Alzheimer’S Disease

Traditional Chinese Medicine (TCM) is a complete medical system that has been practiced for more than 3000 years. Prescription number 1 (PN-1) consists of several Chinese medicines and is designed according to TCM theories to treat patients with neuropsychiatric disorders. The evidence of clinical practice suggests the benefit effects of PN-1 on cognitive deficits of dementia patients. We try to prove and explain this by using contemporary methodology and transgenic animal models of Alzheimer’s disease (AD). The behavioral studies were developed to evaluate the memory of transgenic animals after intragastric administration of PN-1 for 3 months. Amyloid beta-protein (Aβ) neuropathology was quantified using immunohistochemistry and ELISA. The western blotting was used to detect the levels of plasticity associated proteins. The safety of PN-1 on mice was also assessed through multiple parameters. Results showed that PN-1 could effectively relieve learning and memory impairment of transgenic animals. Possible mechanisms showed that PN-1 could significantly reduce plaque burden and Aβlevels and boost synaptic plasticity. Our observations showed that PN-1 could improve learning and memory ability through multiple mechanisms without detectable side effects on mice. We propose that PN-1 is a promising alternative treatment for AD in the future.

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