scholarly journals Severe Gestational Low-Protein Intake Impacts Hippocampal Cellularity, Tau, and Amyloid-β Levels, and Memory Performance in Male Adult Offspring: An Alzheimer-Simile Disease Model?

2021 ◽  
pp. 1-14
Author(s):  
Gabriel Boer Grigoletti-Lima ◽  
Marcelo Gustavo Lopes ◽  
Ana Tereza Barufi Franco ◽  
Aparecida Marcela Damico ◽  
Patrìcia Aline Boer ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Memory Performance ◽  
Memory Function ◽  
Amyloid Β ◽  
Current Data ◽  
Protein Restriction ◽  
Amyloid Β Peptide ◽  
Male Adult ◽  
Cell Numbers ◽  
Maternal Undernutrition

Background: Maternal undernutrition has been associated with psychiatric and neurological disorders characterized by learning and memory impairment. Objective: Considering the lack of evidence, we aimed to analyze the effects of gestational protein restriction on learning and memory function associated with hippocampal cell numbers and neurodegenerative protein content later in life. Methods: Experiments were conducted in gestational low- (LP, 6% casein) or regular-protein (NP, 17% casein) diet intake offspring. Behavioral tests, isolated hippocampal isotropic fractionator cell studies, immunoblotting, and survival lifetime were observed. Results: The birthweight of LP males is significantly reduced relative to NP male progeny, and hippocampal mass increased in 88-week-old LP compared to age-matched NP offspring. The results showed an increased proximity measure in 87-week-old LP compared to NP offspring. Also, LP rats exhibited anxiety-like behaviors compared to NP rats at 48 and 86-wk of life. The estimated neuron number was unaltered in LP rats; however, non-neuron cell numbers increased compared to NP progeny. Here, we showed unprecedented hippocampal deposition of brain-derived neurotrophic factor, amyloid-β peptide (Aβ), and tau protein in 88-week-old LP relative to age-matched NP offspring. Conclusion: To date, no predicted studies showed changes in hippocampal morphological structure in maternal protein-restricted elderly offspring. The current data suggest that gestational protein restriction may accelerate hippocampal function loss, impacting learning/memory performance, and supposedly developing diseases similar to Alzheimer’s disease (AD) in elderly offspring. Thus, we propose that maternal protein restriction could be an elegant and novel method for constructing an AD-like model in adult male offspring.

scholarly journals Precocious hippocampal structural and functional changes in gestational protein-restricted male elderly offspring: an Alzheimer-simile disease model?

2021 ◽  
Author(s):  
Gabriel Boer Grigoletti-Lima ◽  
Marcelo Gustavo Lopes ◽  
Ana Teresa Barufi Franco ◽  
Aparecida Marcela Damico ◽  
Patricia Aline Boer ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Memory Impairment ◽  
Protein Restriction ◽  
Amyloid Peptide ◽  
Proximity Measure ◽  
Functional Changes ◽  
Cell Numbers ◽  
Maternal Undernutrition ◽  
Maternal Protein Restriction ◽  
Age Related

Background: Maternal undernutrition has been associated with psychiatric and neurological disorders characterized by learning and memory impairment. Considering the lack of evidence for this, we aimed to analyze the effects of gestational protein restriction on learning and memory function later in life. This research associates behavioral findings with hippocampal cell numbers and protein content related to neurodegenerative brain disease. Methods: Experiments were conducted in animals subjected to a low-protein (LP, 6% casein) or regular-protein (NP, 17% casein) diet throughout their pregnancy. Behavioral tests, isolated hippocampal isotropic fractionator cell studies, immunoblotting, and survival lifetime tests were performed. The results confirmed that the birthweight of LP male pups significantly reduced relative to NP male pups and that hippocampal mass increased in 88-week-old LP compared to age-matched NP offspring. We used the Morris water maze proximity measure, which is the sum of 10 distances each second between rat position and location of a hidden platform target, as a suitable test for assessing age-related learning or memory impairment in aged offspring. Results: The results showed an increased proximity measure in 87-week-old LP rats (52.6 x 104 ± 10.3 x 104 mm) as compared to NP rats (47.0 x 104 ± 10.6 x 103 mm, p = 0.0007). In addition, LP rats exhibited anxiety-like behaviors compared to NP rats at 48 and 86 weeks of life. Additionally, the estimated neuron number was unaltered in LP rats; however, glial and other cell numbers increased in LP compared to NP rats. Here, we showed unprecedented hippocampal deposition of brain-derived neurotrophic factor, β-amyloid peptide (Aβ), and tau protein in 88-week-old LP compared to age-matched NP offspring. To date, no predicted studies showed changes in hippocampal neuron and glial cell numbers in maternal protein-restricted elderly offspring. The current data suggest that maternal protein restriction has a high impact on lifespan and brain structure, and function. Conclusion: the gestational protein restriction may accelerate hippocampal function loss, impacting learning/memory performance, and supposedly developing diseases similar to Alzheimer's disease (AD) in elderly offspring. Thus, we propose that maternal protein restriction could be a probable, elegant, and novel method for constructing an AD-like model in adult male offspring.

scholarly journals Amyloid-β dimers in the absence of plaque pathology impair learning and synaptic plasticity

Brain ◽  
2015 ◽  
Vol 139 (2) ◽  
pp. 509-525 ◽  
Author(s):  
Andreas Müller-Schiffmann ◽  
Arne Herring ◽  
Laila Abdel-Hafiz ◽  
Aisa N. Chepkova ◽  
Sandra Schäble ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Biological Effects ◽  
Amyloid Β ◽  
Long Term Potentiation ◽  
Amyloid Β Peptide ◽  
Age Related ◽  
Plaque Pathology

Abstract Despite amyloid plaques, consisting of insoluble, aggregated amyloid-β peptides, being a defining feature of Alzheimer’s disease, their significance has been challenged due to controversial findings regarding the correlation of cognitive impairment in Alzheimer’s disease with plaque load. The amyloid cascade hypothesis defines soluble amyloid-β oligomers, consisting of multiple amyloid-β monomers, as precursors of insoluble amyloid-β plaques. Dissecting the biological effects of single amyloid-β oligomers, for example of amyloid-β dimers, an abundant amyloid-β oligomer associated with clinical progression of Alzheimer’s disease, has been difficult due to the inability to control the kinetics of amyloid-β multimerization. For investigating the biological effects of amyloid-β dimers, we stabilized amyloid-β dimers by an intermolecular disulphide bridge via a cysteine mutation in the amyloid-β peptide (Aβ-S8C) of the amyloid precursor protein. This construct was expressed as a recombinant protein in cells and in a novel transgenic mouse, termed tgDimer mouse. This mouse formed constant levels of highly synaptotoxic soluble amyloid-β dimers, but not monomers, amyloid-β plaques or insoluble amyloid-β during its lifespan. Accordingly, neither signs of neuroinflammation, tau hyperphosphorylation or cell death were observed. Nevertheless, these tgDimer mice did exhibit deficits in hippocampal long-term potentiation and age-related impairments in learning and memory, similar to what was observed in classical Alzheimer’s disease mouse models. Although the amyloid-β dimers were unable to initiate the formation of insoluble amyloid-β aggregates in tgDimer mice, after crossbreeding tgDimer mice with the CRND8 mouse, an amyloid-β plaque generating mouse model, Aβ-S8C dimers were sequestered into amyloid-β plaques, suggesting that amyloid-β plaques incorporate neurotoxic amyloid-β dimers that by themselves are unable to self-assemble. Our results suggest that within the fine interplay between different amyloid-β species, amyloid-β dimer neurotoxic signalling, in the absence of amyloid-β plaque pathology, may be involved in causing early deficits in synaptic plasticity, learning and memory that accompany Alzheimer’s disease. 10.1093/brain/awv355_video_abstract awv355_video_abstract

scholarly journals Ameliorative effects of olibanum essential oil on learning and memory in Aβ1-42-induced Alzheimer’s disease mouse model

2020 ◽  
Vol 19 (8) ◽  
pp. 1643-1651
Author(s):  
Zhenzhen Zhang ◽  
Wenhua Chen ◽  
Jie Luan ◽  
Dagui Chen ◽  
Lina Liu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Essential Oil ◽  
Learning And Memory ◽  
Hippocampal Neurons ◽  
Amyloid Β ◽  
Amyloid Plaques ◽  
Morris Water Maze Test ◽  
Amyloid Β Peptide ◽  
Brain Tissues

Purpose: To study the effect of olibanum essential oil (OEO) on learning and memory in Alzheimer’s disease (AD) mouse.Methods: Mice were administered the 42-amino acid form of amyloid β-peptide (Aβ1-42) to induce AD and then treated with OEO at 150, 300, and 600 mg/kg, p.o. for two weeks. Following treatment, the AD mice were assessed by step-down test (SDT), dark avoidance test (DAT), and Morris water maze test (MWM). Blood and brain tissues were collected for biochemical assessments. Gas chromatographymass spectroscopy was used to analyze the main constituents of OEO.Results: The main constituents of OEO were limonene, α-pinene, and 4-terpineol. Treatment with OEO prolonged t latency in SDT and DAT, but decreased error times. Escape latency decreased and crossing times were rose in the MWM following OEO treatment (p < 0.5). Treatment with OEO also enhanced the acetylcholine levels and decreased the acetylcholinesterase levels in serum and brain tissue (p < 0.5). Additionally, OEO reduced amyloid plaques in the hippocampus and protected hippocampal neurons from damage. Furthermore, OEO decreased c-fos expression in  hippocampus tissues from AD mice (p < 0.5).Conclusion: OEO has significant ameliorative effect AD-induced deterioration in learning and memory in AD mouse induced by Aβ1-42. The mechanisms of these effects are related to increased acetylcholine contents, reduction of amyloid plaques, protection of hippocampal neurons, and downregulation of c-fos in brain tissues. The results justify the need for further investigation of candidate drugs derived from OEO for the  management of AD. Keywords: Olibanum, Essential oil, Learning, Memory, AD

scholarly journals Dendrobium alkaloids decrease Aβ by regulating α- and β-secretases in hippocampal neurons of SD rats

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7627 ◽  
Author(s):  
Juan Huang ◽  
Nanqu Huang ◽  
Minghui Zhang ◽  
Jing Nie ◽  
Yunyan Xu ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cell Viability ◽  
Learning And Memory ◽  
Hippocampal Neurons ◽  
Memory Function ◽  
Amyloid Β ◽  
Aging Effects ◽  
Potential Health ◽  
Sd Rats

Background Alzheimer’s disease (AD) is the primary cause of dementia in the elderly. The imbalance between production and clearance of amyloid β (Aβ) is a very early, often initiating factor in AD. Dendrobium nobile Lindl. alkaloids (DNLA) extracted from a Chinese medicinal herb, which have been shown to have anti-aging effects, protected against neuronal impairment in vivo and in vitro. Moreover, we confirmed that DNLA can improve learning and memory function in elderly normal mice, indicating that DNLA has potential health benefits. However, the underlying mechanism is unclear. Therefore, we further explored the effect of DNLA on neurons, which is closely related to learning and memory, based on Aβ. Methods We exposed cultured hippocampal neurons to DNLA to investigate the effect of DNLA on Aβ in vitro. Cell viability was evaluated by MTT assays. Proteins were analyzed by Western blot analysis. Results The cell viability of hippocampal neurons was not changed significantly after treatment with DNLA. But DNLA reduced the protein expression of amyloid precursor protein (APP), disintegrin and metalloprotease 10 (ADAM10), β-site APP cleaving enzyme 1 (BACE1) and Aβ1–42 of hippocampal neurons in rats and increased the protein expression of ADAM17. Conclusions DNLA decreases Aβ by regulating α- and β-secretase in hippocampal neurons of SD rats.

scholarly journals Plasmon-Activated Water Reduces Amyloid Burden and Improves Memory in Animals with Alzheimer’s Disease

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chia-Hsiung Cheng ◽  
Kun-Ju Lin ◽  
Chien-Tai Hong ◽  
Dean Wu ◽  
Hung-Ming Chang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Memory Performance ◽  
Memory Function ◽  
Amyloid Β ◽  
Amyloid Pet ◽  
Amyloid Burden ◽  
Daily Consumption ◽  
Innovative Strategy

Abstract With the great extension of the human lifespan in recent times, many aging diseases have inevitably followed. Dementia is one of the most-commom neurodegenerative aging diseases, in which inflammation-related Alzheimer’s disease (AD) is the most prevalent cause of dementia. Amyloid accumulation in the brain, which occurs before any clinical presentations, might be the first and key step in the development of AD. However, many clinical trials have attempted to remove amyloid from brains of AD patients, but none has so far been successful. Negatively charged plasmon-activated water (PAW) is created by resonantly illuminated gold (Au) nanoparticles (NPs), which reduce the hydrogen-bonded (HB) structure of water. PAW was found to possess anti-oxidative and anti-inflammatory effects. Herein, we report on an innovative strategy to retard the progression of AD by the daily consumption of PAW instead of normal deionized (DI) water. APPswe/PS1dE9 transgenic mice were treated with PAW or DI water from the age of 5 months for the next 9 months. Encouragingly, compared to DI water-treated mice, mice treated with PAW presented better memory performance on a test of novel object recognition and had a significantly lower amyloid burden according to 18F-florbetapir amyloid-PET and phosphorylated (p)-tau burden according to Western blotting and immunohistochemistry measurements. There were no obvious side effects in PAW-treated mice. Collectively, our findings support that PAW was able to reduce the amyloid and p-tau burden and improve memory in an AD mouse model. However, the protein levels of molecules involved in amyloid metabolism and oligomeric amyloid did not change. We propose that the effects of PAW of reducing the amyloid burden and improving memory function cannot be attributed to synthesis/degradation of amyloid-βprotein but probably in preventing aggregation of amyloid-β proteins or other mechanisms, including anti-inflammation. Further applications of PAW in clinical trials to prevent the progression of AD are being designed.

scholarly journals [Gly14]-Humanin Protects Against Amyloid β Peptide-Induced Impairment of Spatial Learning and Memory in Rats

2016 ◽  
Vol 32 (4) ◽  
pp. 374-382 ◽  
Author(s):  
Li Yuan ◽  
Xiao-Jie Liu ◽  
Wei-Na Han ◽  
Qing-Shan Li ◽  
Zhao-Jun Wang ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Spatial Learning ◽  
Amyloid Β ◽  
Spatial Learning And Memory ◽  
Amyloid Β Peptide
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