scholarly journals Loss of drebrin from dendritic spines in hippocampal neurons from Alzheimer's disease model mouse

2020 ◽  
Vol 93 (0) ◽  
pp. 2-P-135
Author(s):  
Noriko Koganezawa ◽  
Yuki Kajita ◽  
Hiroyuki Yamazaki ◽  
Takashi Saito ◽  
Yuko Sekino ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dendritic Spines ◽  
Hippocampal Neurons ◽  
Disease Model ◽  
Model Mouse

scholarly journals Stabilization of dynamic microtubules by mDia1 drives Tau-dependent Aβ1–42 synaptotoxicity

2017 ◽  
Vol 216 (10) ◽  
pp. 3161-3178 ◽  
Author(s):  
Xiaoyi Qu ◽  
Feng Ning Yuan ◽  
Carlo Corona ◽  
Silvia Pasini ◽  
Maria Elena Pero ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Axonal Transport ◽  
Dendritic Spines ◽  
Posttranslational Modifications ◽  
Hippocampal Neurons ◽  
Neuronal Damage ◽  
Driving Factors ◽  
Hyperphosphorylated Tau ◽  
Tau Hyperphosphorylation

Oligomeric Amyloid β1–42 (Aβ) plays a crucial synaptotoxic role in Alzheimer’s disease, and hyperphosphorylated tau facilitates Aβ toxicity. The link between Aβ and tau, however, remains controversial. In this study, we find that in hippocampal neurons, Aβ acutely induces tubulin posttranslational modifications (PTMs) and stabilizes dynamic microtubules (MTs) by reducing their catastrophe frequency. Silencing or acute inhibition of the formin mDia1 suppresses these activities and corrects the synaptotoxicity and deficits of axonal transport induced by Aβ. We explored the mechanism of rescue and found that stabilization of dynamic MTs promotes tau-dependent loss of dendritic spines and tau hyperphosphorylation. Collectively, these results uncover a novel role for mDia1 in Aβ-mediated synaptotoxicity and demonstrate that inhibition of MT dynamics and accumulation of PTMs are driving factors for the induction of tau-mediated neuronal damage.

P1-089: ADMINISTRATION OF BIFIDOBACTERIUM BREV E STRAIN A1 PREVENTS COGNITIVE IMPAIRMENT IN AN ALZHEIMER'S DISEASE MODEL MOUSE

2006 ◽  
Vol 14 (7S_Part_5) ◽  
pp. P305-P305
Author(s):  
Yodai Kobayashi ◽  
Kousuke Shimada ◽  
Eri Mitsuyama ◽  
Tetsuya Kuhara ◽  
Akihito Yasuoka ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Disease Model ◽  
Model Mouse

Effect of Plant Compound Curcumin on the Expression of a-Synuclein in Hippocampal Neurons of APPswe/PS1dE9 Double Transgenic Mice

2013 ◽  
Vol 781-784 ◽  
pp. 643-646
Author(s):  
Xiao Lin ◽  
Li Yu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Hippocampal Neurons ◽  
Neuroprotective Effect ◽  
Disease Model ◽  
Dependent Manner ◽  
Double Transgenic Mice ◽  
Ad Alzheimer’S Disease ◽  
Dose Dependent

In this study, we aim to investigate the effect of curcumin on the expression of a-synuclein in the APPswe/PS1dE9 double transgenic mice. APPswe/PS1dE9 double transgenic mice were used as AD (Alzheimer's disease) model and fed with different concentrations of curcumin every day for 6 months, then immunohistochemistry method were used to detect the expression of a-synuclein in hippocampus of mice. The expression of a-syn in hippocampal neuron was decreased significantly after treated with 0.16g/kg to 1.0g/kg curcumin, the change was apparent in dose-dependent manner (P<0.05). a-synuclein pay an important role in the genesis and development of Alzheimer's disease and decreased level of a-synuclein might contribute to the neuroprotective effect of Curcumin, which may become a new target for the prevention and treatment of Alzheimer's disease.

scholarly journals Extracellular and intraneuronal HMW-AbetaOs represent a molecular basis of memory loss in Alzheimer's disease model mouse

2011 ◽  
Vol 6 (1) ◽  
pp. 20 ◽  
Author(s):  
Ayumi Takamura ◽  
Yasuhide Okamoto ◽  
Takeshi Kawarabayashi ◽  
Tatsuki Yokoseki ◽  
Masao Shibata ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Molecular Basis ◽  
Disease Model ◽  
Memory Loss ◽  
Model Mouse

scholarly journals Clemastine Ameliorates Myelin Deficits via Preventing Senescence of Oligodendrocytes Precursor Cells in Alzheimer’s Disease Model Mouse

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuan-Yuan Xie ◽  
Ting-Ting Pan ◽  
De-en Xu ◽  
Xin Huang ◽  
Yong Tang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Short Term Memory ◽  
Therapeutic Potential ◽  
Disease Model ◽  
Model Mouse ◽  
Oligodendrocyte Precursor ◽  
Myelin Deficits ◽  
M1 Muscarinic

Disrupted myelin and impaired myelin repair have been observed in the brains of patients and various mouse models of Alzheimer’s disease (AD). Clemastine, an H1-antihistamine, shows the capability to induce oligodendrocyte precursor cell (OPC) differentiation and myelin formation under different neuropathological conditions featuring demyelination via the antagonism of M1 muscarinic receptor. In this study, we investigated if aged APPSwe/PS1dE9 mice, a model of AD, can benefit from chronic clemastine treatment. We found the treatment reduced brain amyloid-beta deposition and rescued the short-term memory deficit of the mice. The densities of OPCs, oligodendrocytes, and myelin were enhanced upon the treatment, whereas the levels of degraded MBP were reduced, a marker for degenerated myelin. In addition, we also suggest the role of clemastine in preventing OPCs from entering the state of cellular senescence, which was shown recently as an essential causal factor in AD pathogenesis. Thus, clemastine exhibits therapeutic potential in AD via preventing senescence of OPCs.

scholarly journals New Alzheimer’s disease model mouse specialized for analyzing the function and toxicity of intraneuronal Amyloid β oligomers

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tomoyo Ochiishi ◽  
Masami Kaku ◽  
Kazuyuki Kiyosue ◽  
Motomichi Doi ◽  
Takao Urabe ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Model ◽  
Amyloid Β ◽  
Long Term Potentiation ◽  
Amyloid Β Protein ◽  
Aβ Oligomers ◽  
Term Potentiation ◽  
Model Mouse

AbstractOligomers of intracellular amyloid β protein (Aβ) are strongly cytotoxic and play crucial roles in synaptic transmission and cognitive function in Alzheimer’s disease (AD). However, there is currently no AD model mouse in which to specifically analyze the function of Aβ oligomers only. We have now developed a novel AD model mouse, an Aβ-GFP transgenic mouse (Aβ-GFP Tg), that expresses the GFP-fused human Aβ1-42 protein, which forms only Aβ oligomers within neurons throughout their life. The fusion proteins are expressed mainly in the hippocampal CA1-CA2 region and cerebral cortex, and are not secreted extracellularly. The Aβ-GFP Tg mice exhibit increased tau phosphorylation, altered spine morphology, decreased expressions of the GluN2B receptor and neuroligin in synaptic regions, attenuated hippocampal long-term potentiation, and impaired object recognition memory compared with non-Tg littermates. Interestingly, these dysfunctions have already appeared in 2–3-months-old animals. The Aβ-GFP fusion protein is bioactive and highly toxic, and induces the similar synaptic dysfunctions as the naturally generated Aβ oligomer derived from postmortem AD patient brains and synthetic Aβ oligomers. Thus, Aβ-GFP Tg mouse is a new tool specialized to analyze the function of Aβ oligomers in vivo and to find subtle changes in synapses in early symptoms of AD.

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