Original article Dendritic and spinal alterations of neurons from Edinger-Westphal nucleus in Alzheimer’s disease

Mavroudis, Ioannis; Manani, Marina George; Petrides, Foivos; Petsoglou, Constantina; Njau, Samuel; Costa, Vassiliki; Baloyannis, Stavros J.

doi:10.5114/fn.2014.43791

Cited by 16 publications

(15 citation statements)

References 34 publications

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“…Reduced dendritic arborization, diminished spine numbers, synaptic loss, and neuronal death have been widely reported in AD patients and in animal models of this disease [17, 18, 47, 78–82]. Loss of dendritic complexity and reduced spine densities are also prominent features of AD and correlate significantly with cognitive decline [16].…”

Section: Discussionmentioning

confidence: 99%

STX, a Novel Membrane Estrogen Receptor Ligand, Protects Against Amyloid-β Toxicity

Gray

Zweig

Kawamoto

et al. 2016

JAD

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Because STX is a selective ligand for membrane estrogen receptors, it may be able to confer the beneficial effects of estrogen without eliciting the deleterious side effects associated with activation of the nuclear estrogen receptors. This study evaluates the neuroprotective properties of STX in the context of amyloid-β (Aβ) exposure. MC65 and SH-SY5Y neuroblastoma cell lines, as well as primary hippocampal neurons from wild type (WT) and Tg2576 mice, were used to investigate the ability of STX to attenuate cell death, mitochondrial dysfunction, dendritic simplification, and synaptic loss induced by Aβ. STX prevented Aβ-induced cell death in both neuroblastoma cell lines; it also normalized the decrease in ATP and mitochondrial gene expression caused by Aβ in these cells. Notably, STX also increased ATP content and mitochondrial gene expression in control neuroblastoma cells (in the absence of Aβ). Likewise in primary neurons, STX increased ATP levels and mitochondrial gene expression in both genotypes. In addition, STX treatment enhanced dendritic arborization and spine densities in WT neurons and prevented the diminished outgrowth of dendrites caused by Aβ exposure in Tg2576 neurons. These data suggest that STX can act as an effective neuroprotective agent in the context of Aβ toxicity, improving mitochondrial function as well as dendritic growth and synaptic differentiation. In addition, since STX also improved these endpoints in the absence of Aβ, this compound may have broader therapeutic value beyond Alzheimer’s disease.

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Section: Discussionmentioning

confidence: 99%

STX, a Novel Membrane Estrogen Receptor Ligand, Protects Against Amyloid-β Toxicity

Gray

Zweig

Kawamoto

et al. 2016

JAD

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“…Several studies have suggested that the dysfunction of synapses and dendritic spines precedes neuronal dysfunction and death during AD-induced neurodegeneration (Chabrier et al 2014;Mavroudis et al 2014). These hypotheses are supported by evidence from studies examining various postmortem tissue samples obtained from AD patients, in which a loss of dendritic spines was clearly detected in the hippocampus and other brain areas associated with AD pathology (Knobloch and Mansuy 2008).…”

Section: Discussionmentioning

confidence: 89%

“…; Mavroudis et al . ). These hypotheses are supported by evidence from studies examining various postmortem tissue samples obtained from AD patients, in which a loss of dendritic spines was clearly detected in the hippocampus and other brain areas associated with AD pathology (Knobloch and Mansuy ).…”

Section: Discussionmentioning

confidence: 97%

p120‐catenin is necessary for neuroprotection induced by CDK5 silencing in models of Alzheimer's disease

Uribe-Arias

Posada‐Duque

González-Billault

et al. 2016

Journal of Neurochemistry

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Cyclin-dependent kinase 5 (CDK5) plays important roles in synaptic function. Its unregulated over-activation has been, however, associated with neurodegeneration in Alzheimer’s disease. Our previous studies revealed that CDK5 silencing ameliorates tauopathy and spatial memory impairment in the 3xTgAD mouse model. However, how CDK5 targeting affects synaptic adhesion proteins, such as those involved in the cadherin/catenin system, during learning and memory processes is not completely understood. In the present study, we detected reduced expression of p120 catenin (p120 ctn), N-cadherin, and β-catenin in the brain of human Alzheimer’s disease patients, in addition to a reduced PSD95 and GluN2B protein levels in a 3xTgAD mouse model. Such decrease in synaptic proteins was recovered by CDK5 silencing in mice leading to a better learning and memory performance. Additionally, CDK5 inhibition or knockout increased p120 ctn levels. Moreover in a glutamate-induced excitotoxicity model CDK5 silencing-induced neuroprotection depended on p120 ctn. Together, those findings suggest that p120 ctn plays an important role in the neuronal dysfunction of AD models and contributes to CDK5 silencing-induced neuroprotection and improvement of memory function.

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“…Dendritic spines are tiny protrusions of dendrites that are essential for excitatory synaptic transmission [6,7,22]. AD brains show a marked reduction in synaptic density and a loss of dendritic spines in the cortex and the hippocampus [9,31]. Synaptic impairment is likely to be the major contributor to memory loss in AD [23,41].…”

Section: Discussionmentioning

confidence: 99%

Spatial Training Ameliorates Long-Term Alzheimer's Disease-Like Pathological Deficits by Reducing NLRP3 Inflammasomes in PR5 Mice

et al. 2019

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Recent studies have suggested that cognitive training could delay memory loss in Alzheimer's disease (AD). However, whether and how cognitive training produces long-term benefits remains unclear. Here, 10-month-old PR5 mice were spatially trained in a water maze for 4 consecutive weeks. The novel object recognition test (NORT), Western blots, Golgi staining, and ELISA were used to examine behavioral, biochemical, and pathological measures immediately after training and 3 months later. Immediately after training, we found that spatial training significantly improved cognitive performance; reduced tau neuropathology; increased the expression level of synaptophysin, PSD93, and PSD95 in the hippocampus; and increased the number of dendritic spines in PR5 mice. The expression levels of NLRP3, caspase-1, and interleukin (IL)-1β, which were significantly elevated in PR5 mice, were reversed by spatial training. Interestingly, these effects persisted 3 months later. To further detect the role of NLRP3 in spatial training, PR5/NLRP3−/− mice and PR5/ NLRP3+/− mice were also used in our study. PR5/NLRP3−/− mice showed better cognitive performance than PR5 mice. After 1 week of spatial training, these changes (including those in expression levels of synaptophysin, PSD93, and PSD95; the number of dendritic spines; and caspase-1 and IL-1β content in PR5 mice) could be totally reversed in PR5/NLRP3−/− and PR5/NLRP3+/− mice. In addition, there was a positive correlation between NLRP3 content and the expression levels of caspase-1 and IL-1β. These results show an important role for the NLRP3/caspase-1/IL-1β axis in ameliorating the effect of spatial training on cognitive impairment in PR5 mice.

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Original article Dendritic and spinal alterations of neurons from Edinger-Westphal nucleus in Alzheimer’s disease

Cited by 16 publications

References 34 publications

STX, a Novel Membrane Estrogen Receptor Ligand, Protects Against Amyloid-β Toxicity

STX, a Novel Membrane Estrogen Receptor Ligand, Protects Against Amyloid-β Toxicity

p120‐catenin is necessary for neuroprotection induced by CDK5 silencing in models of Alzheimer's disease

Spatial Training Ameliorates Long-Term Alzheimer's Disease-Like Pathological Deficits by Reducing NLRP3 Inflammasomes in PR5 Mice

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