scholarly journals Intermittent Hypoxia Training Prevents Deficient Learning-Memory Behavior in Mice Modeling Alzheimer's Disease: A Pilot Study

2021 ◽  
Vol 13 ◽  
Author(s):  
Myoung-Gwi Ryou ◽  
Xiaoan Chen ◽  
Ming Cai ◽  
Hong Wang ◽  
Marianna E. Jung ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Spatial Learning ◽  
Water Maze ◽  
Intermittent Hypoxia ◽  
Amyloid Β ◽  
Trophic Factors ◽  
Memory Decline ◽  
Neurobehavioral Function ◽  
Spatial Learning Memory

In mouse models of Alzheimer's disease (AD), normobaric intermittent hypoxia training (IHT) can preserve neurobehavioral function when applied before deficits develop, but IHT's effectiveness after onset of amyloid-β (Aβ) accumulation is unclear. This study tested the hypothesis that IHT improves learning-memory behavior, diminishes Aβ accumulation in cerebral cortex and hippocampus, and enhances cerebrocortical contents of the neuroprotective trophic factors erythropoietin and brain-derived neurotrophic factor (BDNF) in mice manifesting AD traits. Twelve-month-old female 3xTg-AD mice were assigned to untreated 3xTg-AD (n = 6), AD+IHT (n = 6), and AD+sham-IHT (n = 6) groups; 8 untreated wild-type (WT) mice also were studied. AD+IHT mice alternately breathed 10% O2 for 6 min and room air for 4 min, 10 cycles/day for 21 days; AD+sham-IHT mice breathed room air. Spatial learning-memory was assessed by Morris water maze. Cerebrocortical and hippocampal Aβ40 and Aβ42 contents were determined by ELISA, and cerebrocortical erythropoietin and BDNF were analyzed by immunoblotting and ELISA. The significance of time (12 vs. 12 months + 21 days) and treatment (IHT vs. sham-IHT) was evaluated by two-factor ANOVA. The change in swimming distance to find the water maze platform after 21 d IHT (−1.6 ± 1.8 m) differed from that after sham-IHT (+5.8 ± 2.6 m). Cerebrocortical and hippocampal Aβ42 contents were greater in 3xTg-AD than WT mice, but neither time nor treatment significantly affected Aβ40 or Aβ42 contents in the 3xTg-AD mice. Cerebrocortical erythropoietin and BDNF contents increased appreciably after IHT as compared to untreated 3xTg-AD and AD+sham-IHT mice. In conclusion, moderate, normobaric IHT prevented spatial learning-memory decline and restored cerebrocortical erythropoietin and BDNF contents despite ongoing Aβ accumulation in 3xTg-AD mice.

scholarly journals 24(S)-Saringosterol Prevents Cognitive Decline in a Mouse Model for Alzheimer’s Disease

Marine Drugs ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 190
Author(s):  
Nikita Martens ◽  
Melissa Schepers ◽  
Na Zhan ◽  
Frank Leijten ◽  
Gardi Voortman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Cognitive Decline ◽  
Inflammatory Marker ◽  
Amyloid Β ◽  
Liver Fat ◽  
Gas Chromatography Mass Spectrometry ◽  
Memory Decline ◽  
Plaque Load

We recently found that dietary supplementation with the seaweed Sargassum fusiforme, containing the preferential LXRβ-agonist 24(S)-saringosterol, prevented memory decline and reduced amyloid-β (Aβ) deposition in an Alzheimer’s disease (AD) mouse model without inducing hepatic steatosis. Here, we examined the effects of 24(S)-saringosterol as a food additive on cognition and neuropathology in AD mice. Six-month-old male APPswePS1ΔE9 mice and wildtype C57BL/6J littermates received 24(S)-saringosterol (0.5 mg/25 g body weight/day) (APPswePS1ΔE9 n = 20; C57BL/6J n = 19) or vehicle (APPswePS1ΔE9 n = 17; C57BL/6J n = 19) for 10 weeks. Cognition was assessed using object recognition and object location tasks. Sterols were analyzed by gas chromatography/mass spectrometry, Aβ and inflammatory markers by immunohistochemistry, and gene expression by quantitative real-time PCR. Hepatic lipids were quantified after Oil-Red-O staining. Administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice without affecting the Aβ plaque load. Moreover, 24(S)-saringosterol prevented the increase in the inflammatory marker Iba1 in the cortex of APPswePS1ΔE9 mice (p < 0.001). Furthermore, 24(S)-saringosterol did not affect the expression of lipid metabolism-related LXR-response genes in the hippocampus nor the hepatic neutral lipid content. Thus, administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice independent of effects on Aβ load and without adverse effects on liver fat content. The anti-inflammatory effects of 24(S)-saringosterol may contribute to the prevention of cognitive decline.

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 Neuroprotective Effect of Ethanol Extract of Leaves of Malva parviflora against Amyloid-β- (Aβ-) Mediated Alzheimer’s Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Muhammad Aslam ◽  
Ali Akbar Sial
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Superoxide Dismutase ◽  
Water Maze ◽  
Neuroprotective Effect ◽  
Amyloid Β ◽  
Ethanol Extract ◽  
Neuroprotective Activity ◽  
Malva Parviflora ◽  
Lipid Peroxidase

Malva parviflora L. possesses significant antioxidant potential. This study was conducted to evaluate the neuroprotective effect of ethanol extract of the leaves of Malva parviflora against amyloid-β- (Aβ-) mediated Alzheimer’s disease. In Morris water maze model, the extract significantly restored the defected memory of amyloid-β injected mice (P<0.01). The reduced levels of brain antioxidant enzymes such as glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase were also restored significantly to similar levels as seen in normal control mice (P<0.01). The levels of lipid peroxidase were decreased significantly in treatment group mice when compared to Alzheimer group mice (P<0.01). So, this study showed that ethanol extract of the leaves of Malva parviflora possesses neuroprotective activity in mice.

Elevated Tau PET Signal Depends on Abnormal Amyloid Levels and Correlates with Cognitive Impairment in Elderly Persons without Dementia

2020 ◽  
Vol 78 (1) ◽  
pp. 395-404 ◽  
Author(s):  
Rui-Qi Zhang ◽  
Shi-Dong Chen ◽  
Xue-Ning Shen ◽  
Yu-Xiang Yang ◽  
Jia-Ying Lu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Executive Function ◽  
Amyloid Β ◽  
Amyloid Pet ◽  
Elderly Persons ◽  
Cross Sectional ◽  
Memory Decline ◽  
Tau Pet

Background: The recent developed PET ligands for amyloid-β (Aβ) and tau allow these two neuropathological hallmarks of Alzheimer’s disease (AD) to be mapped and quantified in vivo and to be examined in relation to cognition. Objective: To assess the associations among Aβ, tau, and cognition in non-demented subjects. Methods: Three hundred eighty-nine elderly participants without dementia from the Alzheimer’s Disease Neuroimaging Initiative underwent tau and amyloid PET scans. Cross-sectional comparisons and longitudinal analyses were used to evaluate the relationship between Aβ and tau accumulation. The correlations between biomarkers of both pathologies and performance in memory and executive function were measured. Results: Increased amyloid-PET retention was associated with greater tau-PET retention in widespread cortices. We observed a significant tau increase in the temporal composite regions of interest over 24 months in Aβ+ but not Aβ– subjects. Finally, tau-PET retention but not amyloid-PET retention significantly explained the variance in memory and executive function. Higher level of tau was associated with greater longitudinal memory decline. Conclusion: These findings suggested PET-detectable Aβ plaque pathology may be a necessary antecedent for tau-PET signal elevation. Greater tau-PET retention may demonstrate poorer cognition and predict prospective memory decline in non-demented subjects.

scholarly journals Elevated Norepinephrine Metabolism Gauges Alzheimer’s Disease-Related Pathology and Memory Decline

2021 ◽  
Vol 80 (2) ◽  
pp. 521-526
Author(s):  
Joost M. Riphagen ◽  
Maxime van Egroo ◽  
Heidi I.L. Jacobs
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dose Response ◽  
Time Trends ◽  
Amyloid Β ◽  
Hyperphosphorylated Tau ◽  
Memory Clinic ◽  
Memory Decline ◽  
Disease Biomarkers ◽  
Norepinephrine Metabolism

The noradrenergic (NE) locus coeruleus (LC) is vulnerable to hyperphosphorylated tau, and dysregulated NE-metabolism is linked to greater tau and disease progression. We investigated whether elevated NE-metabolism alone predicts memory decline or whether concomitant presence of tau and amyloid-β is required. Among 114 memory clinic participants, time trends (max. six years) showed dose-response declines in learning across groups with elevated NE-metabolite 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) with no, one, or two Alzheimer’s disease biomarkers; and no decline in the low MHPG group. Elevated MHPG is required and sufficient to detect learning declines, supporting a pathophysiologic model including the LC-NE system contributing to initial Alzheimer’s disease-related processes.

scholarly journals Amyloid-β protofibril levels correlate with spatial learning in Arctic Alzheimer’s disease transgenic mice

FEBS Journal ◽  
2009 ◽  
Vol 276 (4) ◽  
pp. 995-1006 ◽  
Author(s):  
Anna Lord ◽  
Hillevi Englund ◽  
Linda Söderberg ◽  
Stina Tucker ◽  
Fredrik Clausen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Spatial Learning ◽  
Amyloid Β
Sign in / Sign up

Export Citation Format

Share Document