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

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.

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Antroquinonol Lowers Brain Amyloid-β Levels and Improves Spatial Learning and Memory in a Transgenic Mouse Model of Alzheimer’s Disease

Scientific Reports ◽

10.1038/srep15067 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 26

Author(s):

Wen-Han Chang ◽

Miles C. Chen ◽

Irene H. Cheng

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Learning And Memory ◽

Transgenic Mouse ◽

Spatial Learning ◽

Amyloid Β ◽

Transgenic Mouse Model ◽

Spatial Learning And Memory ◽

Model Of Alzheimer’S Disease

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Liraglutide protects against amyloid-β protein-induced impairment of spatial learning and memory in rats

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2012.04.009 ◽

2013 ◽

Vol 34 (2) ◽

pp. 576-588 ◽

Cited By ~ 75

Author(s):

Wei-Na Han ◽

Christian Hölscher ◽

Li Yuan ◽

Wei Yang ◽

Xiao-Hui Wang ◽

...

Keyword(s):

Learning And Memory ◽

Spatial Learning ◽

Amyloid Β ◽

Spatial Learning And Memory ◽

Amyloid Β Protein ◽

Β Protein

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Ameliorating Ribosylation-Induced Amyloid-β Pathology by Berberine via Inhibiting mTOR/p70S6K Signaling

Journal of Alzheimer s Disease ◽

10.3233/jad-200995 ◽

2020 ◽

pp. 1-12

Author(s):

Yang-Yang Wang ◽

Qian Yan ◽

Zhen-Ting Huang ◽

Qian Zou ◽

Jing Li ◽

...

Keyword(s):

Signaling Pathway ◽

Learning And Memory ◽

Spatial Learning ◽

Early Stage ◽

Amyloid Β ◽

Mtor Signaling ◽

Immunofluorescence Staining ◽

Morris Water Maze Test ◽

Spatial Learning And Memory ◽

Aβ Production

Background: Berberine (BBR) plays a neuroprotective role in the pathogenesis of Alzheimer’s disease (AD), inhibiting amyloid-β (Aβ) production and promoting Aβ clearance. Advanced glycation end products (AGEs) promote Aβ aggregation and tau hyperphosphorylation. The activation of mTOR signaling occurring at the early stage of AD has a prominent impact on the Aβ production. This work focused on whether BBR regulates the production and clearance of ribosylation-induced Aβ pathology via inhibiting mTOR signaling. Objective: To explore whether BBR ameliorates ribosylation-induced Aβ pathology in APP/PS1 mice. Methods: Western blot and immunofluorescence staining were used to detect the related proteins of the mammalian target of Rapamycin (mTOR) signaling pathway and autophagy, as well as the related kinases of Aβ generation and clearance. Tissue sections and Immunofluorescence staining were used to observe Aβ42 in APP/PS1 mice hippocampal. Morris water maze test was used to measure the spatial learning and memory of APP/PS1 mice. Results: BBR improves spatial learning and memory of APP/PS1 mice. BBR limits the activation of mTOR/p70S6K signaling pathway and enhances autophagy process. BBR reduces the activity of BACE1 and γ-secretase induced by D-ribose, and enhances Aβ-degrading enzymes and Neprilysin, and inhibits the expression of Aβ in APP/PS1 mice. Conclusion: BBR ameliorates ribosylation-induced Aβ pathology via inhibiting mTOR/p70S6K signaling and improves spatial learning and memory of the APP/PS1 mice.

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Microalgae Aurantiochytrium Sp. Increases Neurogenesis and Improves Spatial Learning and Memory in Senescence-Accelerated Mouse-Prone 8 Mice

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.600575 ◽

2021 ◽

Vol 8 ◽

Author(s):

Kazunori Sasaki ◽

Noelia Geribaldi-Doldán ◽

Qingqing Wu ◽

Julie Davies ◽

Francis G. Szele ◽

...

Keyword(s):

Stem Cells ◽

Learning And Memory ◽

Morris Water Maze ◽

Spatial Learning ◽

Water Maze ◽

Amyloid Β ◽

Spatial Learning And Memory ◽

And Function ◽

Samp8 Mice ◽

Senescence Accelerated Mouse

Much attention has recently been focused on nutraceuticals, with minimal adverse effects, developed for preventing or treating neurological diseases such as Alzheimer's disease (AD). The present study was conducted to investigate the potential effect on neural development and function of the microalgae Aurantiochytrium sp. as a nutraceutical. To test neuroprotection by the ethanol extract of Aurantiochytrium (EEA) and a derivative, the n-Hexane layer of EEA (HEEA), amyloid-β-stimulated SH-SY5Y cells, was used as an in vitro AD model. We then assessed the potential enhancement of neurogenesis by EEA and HEEA using murine ex vivo neurospheres. We also administered EEA or HEEA to senescence-accelerated mouse-prone 8 (SAMP8) mice, a non-transgenic strain with accelerated aging and AD-like memory loss for evaluation of spatial learning and memory using the Morris water maze test. Finally, we performed immunohistochemical analysis for assessment of neurogenesis in mice administered EEA. Pretreatment of SH-SY5Y cells with EEA or the squalene-rich fraction of EEA, HEEA, ameliorated amyloid-β-induced cytotoxicity. Interestingly, only EEA-treated cells showed a significant increase in cell metabolism and intracellular adenosine triphosphate production. Moreover, EEA treatment significantly increased the number of neurospheres, whereas HEEA treatment significantly increased the number of β-III-tubulin+ young neurons and GFAP+ astrocytes. SAMP8 mice were given 50 mg/kg EEA or HEEA orally for 30 days. EEA and HEEA decreased escape latency in the Morris water maze in SAMP8 mice, indicating improved memory. To detect stem cells and newborn neurons, we administered BrdU for 9 days and measured BrdU+ cells in the dentate gyrus, a neurogenic stem cell niche of the hippocampus. In SAMP8 mice, EEA rapidly and significantly increased the number of BrdU+GFAP+ stem cells and their progeny, BrdU+NeuN+ mature neurons. In conclusion, our data in aggregate indicate that EEA and its constituents could be developed into a nutraceutical for promoting brain health and function against several age-related diseases, particularly AD.

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Berberine Promotes TREM2-Dependent Phagocytosis of Amyloid-β By Microglia

10.21203/rs.3.rs-534325/v1 ◽

2021 ◽

Author(s):

Yang-Yang Wang ◽

Zhen-Ting Huang ◽

Qian Zou ◽

Yin-Shuang Pu ◽

Ming-Hao Yuan ◽

...

Keyword(s):

Learning And Memory ◽

Spatial Learning ◽

Microglial Activation ◽

Amyloid Β ◽

Spatial Learning And Memory ◽

Pathological Feature ◽

Bv2 Cells ◽

Aβ Clearance

Abstract Background: The production and accumulation of amyloid-β (Aβ) is the most important pathological feature of Alzheimer’s Disease (AD), and the deficiency of Aβ clearance contributes to the progression of AD. TREM2-dependent microglial activation may be the key to Aβ clearance. BBR plays the neuroprotective role in the progression of AD by inhibiting Aβ production and promoting Aβ degradation. However, the specific relationship between BBR and microglial activation remains unclear. Thus, we aimed to investigate whether BBR can inhibit the pathological progression of Aβ in AD by changing the phenotype of microglia.Methods: Western blot and Immunofluorescence staining were applied to detect the effects of BBR on the transformation of resting microglia to different phenotypes. ELISA, Immunohistochemistry and Immunofluorescence were used to detect the effect of BBR on microglial phagocytosis of Aβ. Morris water maze (MWM) test was applied to test the effect of BBR on the spatial learning and memory of experimental animals.Results: Firstly, BBR promoted the phagocytosis of Aβ1-42 by BV2 cells. Secondly, BBR promoted the changes of microglia to phenotypes M2 and DAM in vivo and in vitro, which were in close proximity to Aβ and reduced Aβ aggregation. Finally, BBR ameliorated spatial learning and memory impairment in APP/PS1 mice.Conclusion: BBR could enhance the phagocytosis of microglia, which decreased Aβ level and improved the spatial learning and memory of APP/PS1 mice.

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