scholarly journals Lactobacillus plantarum GKM3 Promotes Longevity, Memory Retention, and Reduces Brain Oxidation Stress in SAMP8 Mice

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2860
Author(s):  
Shih-Wei Lin ◽  
You-Shan Tsai ◽  
Yen-Lien Chen ◽  
Ming-Fu Wang ◽  
Chin-Chu Chen ◽  
...  
Keyword(s):  
Lactobacillus Plantarum ◽  
Amyloid Β ◽  
Aging Effect ◽  
Amyloid Β Protein ◽  
Memory Retention ◽  
Mice Model ◽  
Oxidation Stress ◽  
Avoidance Test ◽  
Age Related ◽  
Samp8 Mice

(1) Background: An age-related cognitive decline is commonly affecting the life of elderly with symptoms involved in progressive impairments to memory and learning. It has been proposed that probiotics could modulate age-related neurological disorders via the gut–brain axis. (2) Methods: To investigate the anti-aging effect of probiotic Lactobacillus plantarum GKM3, both survival tests and cognitive experiments were conducted in the SAMP8 mice model. The six-month-old SAMP8 (n = 20 in each gender) were fed with probiotic GKM3 at a dosage of 5.1 × 109 and 1.0 × 109 cfu/ kg B.W./day until their natural death. Then, the life span was investigated. Three-month-old SAMP8 (n = 10 in each gender) were administered GKM3 for 14 weeks. Then, the behavior tests and oxidation parameters were recorded. (3) Results: GKM3 groups showed significantly increased latency in the passive avoidance test and time of successful avoidance in the active avoidance test. The TBARS and 8-OHdG from mice brains also showed a significant reduction in the groups treated with GKM3. In addition, lower accumulation of the amyloid-β protein was found in SAMP8 mice brains with the supplement of GKM3. (4) Conclusions: These results indicated that L. plantarum GKM3 delayed the process of aging, alleviated age-related cognitive impairment, and reduced oxidative stress.

scholarly journals Memory Deficits in APP23/Abca1+/− Mice Correlate with the Level of Aβ Oligomers

ASN NEURO ◽  
2009 ◽  
Vol 1 (2) ◽  
pp. AN20090015 ◽  
Author(s):  
Iliya Lefterov ◽  
Nicholas F Fitz ◽  
Andrea Cronican ◽  
Preslav Lefterov ◽  
Matthias Staufenbiel ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Density Lipoprotein ◽  
Memory Deficits ◽  
Specific Pattern ◽  
Amyloid Β Protein ◽  
Memory Retention ◽  
Dot Blot ◽  
Aβ Oligomers ◽  
Characteristic Region ◽  
Ca1 Region

ABCA1, a member of the ATP-binding cassette family of transporters, lipidates ApoE (apolipoprotein A) and is essential for the generation of HDL (high-density lipoprotein)-like particles in the CNS (central nervous system). Lack of Abca1 increases amyloid deposition in several AD (Alzheimer's disease) mouse models. We hypothesized that deletion of only one copy of Abca1 in APP23 (where APP is amyloid precursor protein) AD model mice will aggravate memory deficits in these mice. Using the Morris Water Maze, we demonstrate that 2-year-old Abca1 heterozygous APP23 mice (referred to as APP23/het) have impaired learning during acquisition, and impaired memory retention during the probe trial when compared with age-matched wild-type mice (referred to as APP23/wt). As in our previous studies, the levels of ApoE in APP23/het mice were decreased, but the differences in the levels of A β and thioflavin-S-positive plaques between both groups were insignificant. Importantly, dot blot analysis demonstrated that APP23/het mice have a significantly higher level of soluble A11-positive A β (amyloid β protein) oligomers compared with APP23/wt which correlated negatively with cognitive performance. To confirm this finding, we performed immunohistochemistry with the A11 antibody, which revealed a significant increase of All-positive oligomer structures in the CA1 region of hippocampi of APP23/het. This characteristic region-specific pattern of A11 staining was age-dependent and was missing in younger APP23 mice lacking Abca1. In contrast, the levels of A β*56, as well as other low-molecular-mass A β oligomers, were unchanged among the groups. Overall, the results of the present study demonstrate that in aged APP23 mice memory deficits depend on Abca1 and are likely to be mediated by the amount of A β oligomers deposited in the hippocampus.

scholarly journals Activated microglia-induced neuroinflammatory cytokines lead to photoreceptor apoptosis in age-related macular degeneration-like mice model

2020 ◽  
Author(s):  
Jing Wu ◽  
Ge Gao ◽  
Fanjun Shi ◽  
Chaoyang Zhang ◽  
Hai Xie ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Inflammatory Cytokines ◽  
Critical Role ◽  
Amyloid Β ◽  
Mapk Signaling ◽  
Microglia Activation ◽  
Age Related Macular Degeneration ◽  
Mice Model ◽  
Activated Microglia ◽  
Age Related

Abstract Background Age-related macular degeneration (AMD) is mainly characterized by progressive deposits of drusen and photoreceptor apoptosis. Due to amyloid β (Aβ) is the main component of drusen, there is a great possibility that Aβ-induced activated microglia leads to inflammation, and plays a critical role in the pathogenesis of AMD. However, the relationship between activated microglia-mediated neuroinflammatory cytokines and photoreceptor apoptosis still remains unclarified. Results In this study, we demonstrated that subretinal injection of Aβ1−42 induced the microglia activation and increased inflammatory cytokines, gave rise to photoreceptor apoptosis in mice. Our results were verified in vitro by co-culture of Aβ1−42 activated primary microglia and photoreceptor cell line 661W, and we also performed that p38 MAPK signaling pathway was involved in Aβ1−42 induced microglia activation and inflammatory cytokines release. Conclusions Overall, our findings indicated that activated microglia-mediated neuroinflammatory cytokines contributed to photoreceptor apoptosis under the stimulation of Aβ1−42. Moreover, this study will provide a potential preventive and therapeutic approach for AMD treatment.

448 Age-related amyloid β protein accumulation induces cellular death and macrophage activation

1996 ◽  
Vol 17 (4) ◽  
pp. S111-S112
Author(s):  
M. Shoji ◽  
T. Kawarabayashi ◽  
Y. Igeta ◽  
Y. Tomidokoro ◽  
K. Ishiguro ◽  
...  
Keyword(s):  
Macrophage Activation ◽  
Amyloid Β ◽  
Protein Accumulation ◽  
Amyloid Β Protein ◽  
Cellular Death ◽  
Age Related ◽  
Β Protein

scholarly journals AβPP-induced UPR Transcriptomic Signature of Glial Cells to Oxidative Stress as an Adaptive Mechanism to Preserve Cell Function and Survival

2018 ◽  
Vol 15 (7) ◽  
pp. 643-654 ◽  
Author(s):  
Naima Chalour ◽  
Agathe Maoui ◽  
Patrice Rat ◽  
France Massicot ◽  
Melody Dutot ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
Cell Function ◽  
Amyloid Β ◽  
Redox Status ◽  
Age Related Macular Degeneration ◽  
Amyloid Β Protein ◽  
Major Genes ◽  
Age Related ◽  
Induced Apoptosis

Background: Alzheimer's disease (AD) and age-related macular degeneration (AMD) present similarities, particularly with respect to oxidative stress, including production of 4-Hydroxy-2- nonenal (HNE). AMD has been named the AD in the eye. The Müller cells (MC) function as a principal glia of the retina and maintain water/potassium, glutamate homeostasis and redox status. Any MC dysfunction results in retinal neurodegeneration. Objectives: We investigated the effects of HNE in human MC. Results: HNE induced an increase of the reactive oxygen species associated with mitochondrial dysfunction and apoptosis. HNE induced endoplasmic reticulum (ER) stress (upregulation of GRP78/Bip, and the proapoptotic factor, CHOP). HNE also impaired expression of genes controlling potassium homeostasis (KCNJ10), glutamate detoxification (GS), and the visual cycle (RLBP1). MC adaptive response to HNE included upregulation of amyloid-β protein precursor (AβPP). To determine the role of AβPP, we overexpressed AβPP in MC. Overexpression of AβPP induced strong antioxidant and anti-ER stress (PERK downregulation and GADD34 upregulation) responses accompanied by activation of the prosurvival branch of the unfolded protein response. It was also associated with upregulation of major genes involved in MC-controlled retinal homeostasis (KCNJ10, GS, and RLBP1) and protection against HNE-induced apoptosis. Therefore, AβPP is an ER and oxidative stress responsive molecule, and is able to stimulate the transcription of major genes involved in MC functions impaired by HNE. Conclusion: Our study suggests that targeting oxidative and ER stress might be a potential therapeutic strategy against glia impairment in AMD and AD, in light of the common features between the two pathologies.

Exposure to Traffic-Generated Pollutants Exacerbates the Expression of Factors Associated with the Pathophysiology of Alzheimer’s Disease in Aged C57BL/6 Wild-Type Mice

2020 ◽  
Vol 78 (4) ◽  
pp. 1453-1471
Author(s):  
Tyler D. Armstrong ◽  
Usa Suwannasual ◽  
Conner L. Kennedy ◽  
Akshaykumar Thasma ◽  
Leah J. Schneider ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Environmental Pollutants ◽  
Amyloid Β ◽  
At1 Receptor ◽  
Aged Mouse ◽  
Amyloid Β Protein ◽  
Ca1 Region ◽  
Age Related

Background: Multiple studies report a strong correlation between traffic-generated air pollution-exposure and detrimental outcomes in the central nervous system (CNS), including Alzheimer’s disease (AD). Incidence of AD is rapidly increasing and, worldwide, many live in regions where pollutants exceed regulatory standards. Thus, it is imperative to identify environmental pollutants that contribute to AD, and the mechanisms involved. Objective: We investigated the effects of mixed gasoline and diesel engine emissions (MVE) on the expression of factors involved in progression of AD in the hippocampus and cerebrum in a young versus aged mouse model. Methods: Young (2 months old) and aged (18 months old) male C57BL/6 mice were exposed to either MVE (300μg/m3 PM) or filtered air (FA) for 6 h/d, 7 d/wk, for 50 d. Immunofluorescence and RT-qPCR were used to quantify oxidative stress (8-OHdG) and expression of amyloid-β protein precursor (AβPP), β secretase (BACE1), amyloid-β (Aβ), aryl hydrocarbon receptor (AhR), cytochrome P450 (CYP) 1B1, angiotensin-converting enzyme (ACE1), and angiotensin II type 1 (AT1) receptor in the cerebrum and hippocampus, in addition to cerebral microvascular tight junction (TJ) protein expression. Results: We observed age-related increases in oxidative stress, AhR, CYP1B1, Aβ, BACE1, and AT1 receptor in the CA1 region of the hippocampus, and elevation of cerebral AβPP, AhR, and CYP1B1 mRNA, associated with decreased cerebral microvascular TJ protein claudin-5. MVE-exposure resulted in further promotion of oxidative stress, and significant increases in AhR, CYP1B1, BACE1, ACE1, and Aβ, compared to the young and aged FA-exposed mice. Conclusion: Such findings suggest that MVE-exposure exacerbates the expression of factors in the CNS associated with AD pathogenesis in aged populations.

Age-Related Changes in the Synaptic Density of Amyloid-β Protein Precursor and Secretases in the Human Cerebral Cortex

2016 ◽  
Vol 52 (4) ◽  
pp. 1209-1214 ◽  
Author(s):  
Anna Pliássova ◽  
Paula M. Canas ◽  
Ana Carolina Xavier ◽  
Beatriz S. da Silva ◽  
Rodrigo A. Cunha ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Human Cerebral Cortex ◽  
Synaptic Density ◽  
Protein Precursor ◽  
Age Related ◽  
Β Protein ◽  
Age Related Changes

scholarly journals Amelioration of BPSD-Like Phenotype and Cognitive Decline in SAMP8 Mice Model Accompanied by Molecular Changes after Treatment with I2-Imidazoline Receptor Ligand MCR5

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 475
Author(s):  
Foteini Vasilopoulou ◽  
Andrea Bagan ◽  
Sergio Rodriguez-Arevalo ◽  
Carmen Escolano ◽  
Christian Griñán-Ferré ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Glycogen Synthase ◽  
Growth Factor Receptor ◽  
Adenosine Monophosphate ◽  
Serotoninergic System ◽  
Mice Model ◽  
Necrosis Factor Alpha ◽  
Cognitive Improvement ◽  
Age Related ◽  
Samp8 Mice

Behavioural and psychological symptoms of dementia (BPSD), including fear-anxiety- and depressive-like behaviour, are present in Alzheimer’s disease (AD), together with memory decline. I2-imidazoline receptors (I2-IRs) have been associated with neuropsychiatric and neurodegenerative disorders, further, I2-IR ligands have demonstrated a neuroprotective role in the central nervous system (CNS). In this study, we assessed the effect of the I2-IR ligand MCR5 on both cognitive and non-cognitive symptoms in the Senescence accelerated mice prone 8 (SAMP8) mouse model. Oral administration of I2-IR ligand MCR5 (5 mg/kg/day for four weeks) in 10-month SAMP8 mice ameliorated both BPSD-like phenotype and cognitive decline by attenuating depressive-like behaviour, reducing fear-anxiety-like behaviour and improving cognitive performance using different tasks. Interaction of I2-IR ligand MCR5 with serotoninergic system did not account for behavioural or cognitive improvement, although changes in molecular pathways underlying depression and anxiety phenotype were observed. MCR5 increased levels of p-AKT, phosphorylated glycogen synthase kinase 3 β (GSK3β) at Ser9 and phosphorylated mammalian target of rapamycin complex 1 (mTORC1) levels in SAMP8 treated mice compared to SAMP8 control. Moreover, MCR5 treatment altered N-methyl-d-aspartate receptor (NMDA) 2B phosphorylation, and decreased the protein levels of phosphorylated cyclin-dependent kinase 5 (p-CDK5) and dopamine- and cyclic adenosine monophosphate (cAMP)-regulated phosphoprotein of Mr 32 kDa phosphorylated at Thr75 (p-DARPP32), with a parallel increase in protein kinase A (PKA) and p-cAMP response element-binding (pCREB) levels. Consistent with these changes MCR5 attenuated neuroinflammation by decreasing expression of pro-inflammatory markers such as Tumor necrosis factor-alpha (Tnf-α), Interleukin 1β (Il-1β), Interleukin 6 (Il-6), and promoted synaptic plasticity by increasing levels of postsynaptic density protein 95 (PSD95) as well as ameliorating tropomyosin-related kinase B (TrkB) and nerve growth factor receptor (NGFR) signalling. Collectively, these results increase the potential of highly selective I2-IR ligands as therapeutic agents in age-related BPSD and cognitive alterations.

scholarly journals Mechanism of anti-dementia effects of mangiferin in a senescence accelerated mouse (SAMP8) model

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Zhengcai Du ◽  
Fangcao Fanshi ◽  
Yu-Heng Lai ◽  
Jung-Ren Chen ◽  
Erwei Hao ◽  
...  
Keyword(s):  
Mouse Model ◽  
Learning And Memory ◽  
Hippocampal Neurons ◽  
Amyloid Β ◽  
Memory Retention ◽  
Samp8 Mouse ◽  
Mango Leaves ◽  
Samp8 Mice ◽  
The Brain ◽  
Senescence Accelerated Mouse

Abstract Mangiferin (2-β-d-glucopyranosyl-1,3,6,7-tetrahydroxy-9H-xanthen-9-one), a xanthanoid, is one of the major compounds isolated from mango leaves and bark fruit. Previous studies have identified several properties of mangiferin, such as preventing microbial growth, reducing oxidative stress and helping reduce risk of diabetes. The aim of the present study is to explore the potential anti-dementia effects of Mangiferin in a senescence-accelerated mouse prone 8 (SAMP8) mouse model. Morris water maze (MWM) test showed that mangiferin significantly improved the learning and memory retention in SAMP8 mice. In addition, mangiferin reduced the damage in hippocampal neurons and mitochondria, and decreased the expression of amyloid-β (Aβ1-40 and Aβ1-42); however, no influence on the expression of amyloid precursor protein (APP) within the brain of SAMP8 mice. Moreover, Mangiferin inhibited lipid peroxidation (LPO). In conclusion, we provided evidences to show that mangiferin significantly restored the learning and memory impairment in the SAMP8 mouse model, and reduced the pathological injury in hippocampal by modulating lipid oxidation and amyloid-β deposition in the brain.

scholarly journals Mechanisms of Hydrogen Sulfide against the Progression of Severe Alzheimer’s Disease in Transgenic Mice at Different Ages

Pharmacology ◽  
2018 ◽  
Vol 103 (1-2) ◽  
pp. 50-60 ◽  
Author(s):  
Eleonora Vandini ◽  
Alessandra Ottani ◽  
Davide Zaffe ◽  
Anita Calevro ◽  
Fabrizio Canalini ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hydrogen Sulfide ◽  
Amyloid Β ◽  
Mice Model ◽  
Morphological Alterations ◽  
Age Related ◽  
Preclinical Ad ◽  
Different Ages ◽  
The Brain

Backgroud: Alzheimer disease is an age-related severe neurodegenerative pathology. The level of the third endogenous gas, hydrogen sulfide (H2S), is decreased in the brain of Alzheimer’s disease (AD) patients compared with the brain of the age-matched normal individuals; also, plasma H2S levels are negatively correlated with the severity of AD. Recently, we have demonstrated that systemic H2S injections are neuroprotective in an early phase of preclinical AD. Objectives: This study focuses on the possible neuroprotection of a chronic treatment with an H2S donor and sulfurous water (rich of H2S) in a severe transgenic 3×Tg-AD mice model. Method: 3×Tg-AD mice at 2 different ages (6 and 12 months) were daily treated intraperitoneally with an H2S donor and sulfurous water (rich of H2S) for 3 months consecutively. We investigated the cognitive ability, brain morphological alterations, amyloid/tau cascade, excitotoxic, inflammatory and apoptotic responses. Results: Three months of treatments with H2S significantly protected against impairment in learning and memory in a severe 3×Tg-AD mice model, at both ages studied, and reduced the size of Amyloid β plaques with preservation of the morphological picture. This neuroprotection appeared mainly in the cortex and hippocampus, associated with reduction in activity of c-jun N-terminal kinases, extracellular signal-regulated kinases and p38, which have an established role not only in the phosphorylation of tau protein but also in the inflammatory and excitotoxic response. Conclusion: Our findings indicate that appropriate treatments with various sources of H2S, might represent an innovative approach to counteract early and severe AD progression in humans.

scholarly journals Protofibrils of Amyloid-β are Important Targets of a Disease-Modifying Approach for Alzheimer’s Disease

2020 ◽  
Vol 21 (3) ◽  
pp. 952 ◽  
Author(s):  
Kenjiro Ono ◽  
Mayumi Tsuji
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuronal Damage ◽  
Membrane Integrity ◽  
Reactive Oxygen Species Generation ◽  
Amyloid Β ◽  
Plaque Burden ◽  
Amyloid Β Protein ◽  
Age Related ◽  
Culture Models

Worldwide, Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease and is characterized by unique pathological hallmarks in the brain, including plaques composed of amyloid β-protein (Aβ) and neurofibrillary tangles of tau protein. Genetic studies, biochemical data, and animal models have suggested that Aβ is responsible for the pathogenesis of AD (i.e., the amyloid hypothesis). Indeed, Aβ molecules tend to aggregate, forming oligomers, protofibrils, and mature fibrils. However, while these Aβ species form amyloid plaques of the type implicated in AD neurodegeneration, recent clinical trials designed to reduce the production of Aβ and/or the plaque burden have not demonstrated clinical efficacy. In addition, recent studies using synthetic Aβ peptides, cell culture models, Arctic transgenic mice, and human samples of AD brain tissues have suggested that the pre-fibrillar forms of Aβ, particularly Aβ protofibrils, may be the most critical species, compared with extracellular fibrillar forms. We recently reported that protofibrils of Aβ1-42 disturbed membrane integrity by inducing reactive oxygen species generation and lipid peroxidation, resulting in decreased membrane fluidity, intracellular calcium dysregulation, depolarization, and synaptic toxicity. Therefore, the therapeutic reduction of protofibrils may prevent the progression of AD by ameliorating neuronal damage and cognitive dysfunction through multiple mechanisms.

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