scholarly journals Cyclooxygenase-2 inhibition improves amyloid-β-mediated suppression of memory and synaptic plasticity

Brain ◽  
2008 ◽  
Vol 131 (3) ◽  
pp. 651-664 ◽  
Author(s):  
Linda A. Kotilinek ◽  
Marcus A. Westerman ◽  
Qinwen Wang ◽  
Kimberly Panizzon ◽  
Giselle P. Lim ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Amyloid Β ◽  
Cyclooxygenase 2

Multi-scale modeling of altered synaptic plasticity related to Amyloid β effects

2017 ◽  
Vol 93 ◽  
pp. 230-239 ◽  
Author(s):  
Takumi Matsuzawa ◽  
László Zalányi ◽  
Tamás Kiss ◽  
Péter Érdi
Keyword(s):  
Synaptic Plasticity ◽  
Amyloid Β ◽  
Multi Scale ◽  
Scale Modeling ◽  
Multi Scale Modeling

scholarly journals Postnatal changes in constitutive cyclooxygenase‑2 expression in the mice hippocampus and its function in synaptic plasticity

2019 ◽  
Author(s):  
Hyo Young Jung ◽  
Dae Young Yoo ◽  
Sung Min Nam ◽  
Jong Whi Kim ◽  
Woosuk Kim ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Cyclooxygenase 2

Synaptic memory mechanisms: Alzheimer's disease amyloid β-peptide-induced dysfunction

2007 ◽  
Vol 35 (5) ◽  
pp. 1219-1223 ◽  
Author(s):  
M.J. Rowan ◽  
I. Klyubin ◽  
Q. Wang ◽  
N.W. Hu ◽  
R. Anwyl
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Nitrosative Stress ◽  
Amyloid Β ◽  
Long Term Potentiation ◽  
Amyloid Β Peptide ◽  
Aβ Oligomers ◽  
Aβ Amyloid

There is growing evidence that mild cognitive impairment in early AD (Alzheimer's disease) may be due to synaptic dysfunction caused by the accumulation of non-fibrillar, oligomeric Aβ (amyloid β-peptide), long before widespread synaptic loss and neurodegeneration occurs. Soluble Aβ oligomers can rapidly disrupt synaptic memory mechanisms at extremely low concentrations via stress-activated kinases and oxidative/nitrosative stress mediators. Here, we summarize experiments that investigated whether certain putative receptors for Aβ, the αv integrin extracellular cell matrix-binding protein and the cytokine TNFα (tumour necrosis factor α) type-1 death receptor mediate Aβ oligomer-induced inhibition of LTP (long-term potentiation). Ligands that neutralize TNFα or genetic knockout of TNF-R1s (type-1 TNFα receptors) prevented Aβ-triggered inhibition of LTP in hippocampal slices. Similarly, antibodies to αv-containing integrins abrogated LTP block by Aβ. Protection against the synaptic plasticity-disruptive effects of soluble Aβ was also achieved using systemically administered small molecules targeting these mechanisms in vivo. Taken together, this research lends support to therapeutic trials of drugs antagonizing synaptic plasticity-disrupting actions of Aβ oligomers in preclinical AD.

scholarly journals Amyloid-β as a Modulator of Synaptic Plasticity

2010 ◽  
Vol 22 (3) ◽  
pp. 741-763 ◽  
Author(s):  
Mordhwaj S. Parihar ◽  
Gregory J. Brewer
Keyword(s):  
Synaptic Plasticity ◽  
Amyloid Β

Non-selective NSAIDs improve the amyloid-β-mediated suppression of memory and synaptic plasticity

2015 ◽  
Vol 132 ◽  
pp. 33-41 ◽  
Author(s):  
Jafar Doost Mohammadpour ◽  
Narges Hosseinmardi ◽  
Mahyar Janahmadi ◽  
Yaghoub Fathollahi ◽  
Fereshteh Motamedi ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Amyloid Β

scholarly journals Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory

2008 ◽  
Vol 14 (8) ◽  
pp. 837-842 ◽  
Author(s):  
Ganesh M Shankar ◽  
Shaomin Li ◽  
Tapan H Mehta ◽  
Amaya Garcia-Munoz ◽  
Nina E Shepardson ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Protein Dimers ◽  
Β Protein

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 GLP-1 analogue CJC-1131 prevents amyloid β protein-induced impirments of spatial memory and synaptic plasticity in rats

2017 ◽  
Vol 326 ◽  
pp. 237-243 ◽  
Author(s):  
Sheng-Xiao Zhang ◽  
Hong-Yan Cai ◽  
Xiao-Wen Ma ◽  
Li Yuan ◽  
Jun Zhang ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Spatial Memory ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Β Protein

scholarly journals Amyloid-beta mediates homeostatic synaptic plasticity

2020 ◽  
Author(s):  
Christos Galanis ◽  
Meike Fellenz ◽  
Denise Becker ◽  
Charlotte Bold ◽  
Stefan F. Lichtenthaler ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Granule Cells ◽  
Amyloid Β ◽  
Physiological Role ◽  
Homeostatic Plasticity ◽  
App Processing ◽  
Brain Physiology ◽  
Homeostatic Synaptic Plasticity ◽  
Organotypic Tissue

ABSTRACTThe physiological role of the amyloid-precursor protein (APP) is insufficiently understood. Recent work has implicated APP in the regulation of synaptic plasticity. Substantial evidence exists for a role of APP and its secreted ectodomain APPsα in Hebbian plasticity. Here, we addressed the relevance of APP in homeostatic synaptic plasticity using organotypic tissue cultures of APP−/− mice. In the absence of APP, dentate granule cells failed to strengthen their excitatory synapses homeostatically. Homeostatic plasticity is rescued by amyloid-β (Aβ) and not by APPsα, and it is neither observed in APP+/+ tissue treated with β- or γ-secretase inhibitors nor in synaptopodin-deficient cultures lacking the Ca2+-dependent molecular machinery of the spine apparatus. Together, these results suggest a role of APP processing via the amyloidogenic pathway in homeostatic synaptic plasticity, representing a function of relevance for brain physiology as well as for brain states associated with increased Aβ levels.

scholarly journals Seizure-Induced Regulations of Amyloid-β, STEP61, and STEP61Substrates Involved in Hippocampal Synaptic Plasticity

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Sung-Soo Jang ◽  
Sara E. Royston ◽  
Gunhee Lee ◽  
Shuwei Wang ◽  
Hee Jung Chung
Keyword(s):  
Synaptic Plasticity ◽  
Neurodegenerative Disorder ◽  
Tyrosine Phosphatase ◽  
Amyloid Β ◽  
Epileptic Seizures ◽  
Network Activity ◽  
Extracellular Signal ◽  
Nmdar Subunit ◽  
Hippocampal Network ◽  
Electroconvulsive Seizures

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline. Pathologic accumulation of soluble amyloid-β(Aβ) oligomers impairs synaptic plasticity and causes epileptic seizures, both of which contribute to cognitive dysfunction in AD. However, whether seizures could regulate Aβ-induced synaptic weakening remains unclear. Here we show that a single episode of electroconvulsive seizures (ECS) increased protein expression of membrane-associated STriatal-Enriched protein tyrosine Phosphatase (STEP61) and decreased tyrosine-phosphorylation of its substrates N-methyl D-aspartate receptor (NMDAR) subunit GluN2B and extracellular signal regulated kinase 1/2 (ERK1/2) in the rat hippocampus at 2 days following a single ECS. Interestingly, a significant decrease in ERK1/2 expression and an increase in APP and Aβlevels were observed at 3-4 days following a single ECS when STEP61level returned to the baseline. Given that pathologic levels of Aβincrease STEP61activity and STEP61-mediated dephosphorylation of GluN2B and ERK1/2 leads to NMDAR internalization and ERK1/2 inactivation, we propose that upregulation of STEP61and downregulation of GluN2B and ERK1/2 phosphorylation mediate compensatory weakening of synaptic strength in response to acute enhancement of hippocampal network activity, whereas delayed decrease in ERK1/2 expression and increase in APP and Aβexpression may contribute to the maintenance of this synaptic weakening.

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