scholarly journals Synapses and Dendritic Spines as Pathogenic Targets in Alzheimer’s Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Wendou Yu ◽  
Bingwei Lu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Learning And Memory ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Molecular Mechanisms ◽  
Excitatory Synapses ◽  
Dendritic Shaft ◽  
Spine Pathology ◽  
Dynamic Structures

Synapses are sites of cell-cell contacts that transmit electrical or chemical signals in the brain. Dendritic spines are protrusions on dendritic shaft where excitatory synapses are located. Synapses and dendritic spines are dynamic structures whose plasticity is thought to underlie learning and memory. No wonder neurobiologists are intensively studying mechanisms governing the structural and functional plasticity of synapses and dendritic spines in an effort to understand and eventually treat neurological disorders manifesting learning and memory deficits. One of the best-studied brain disorders that prominently feature synaptic and dendritic spine pathology is Alzheimer’s disease (AD). Recent studies have revealed molecular mechanisms underlying the synapse and spine pathology in AD, including a role for mislocalized tau in the postsynaptic compartment. Synaptic and dendritic spine pathology is also observed in other neurodegenerative disease. It is possible that some common pathogenic mechanisms may underlie the synaptic and dendritic spine pathology in neurodegenerative diseases.

Fluoxetine Protects against Dendritic Spine Loss in Middle-aged APPswe/PSEN1dE9 Double Transgenic Alzheimer’s Disease Mice

2020 ◽  
Vol 17 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Jing Ma ◽  
Yuan Gao ◽  
Wei Tang ◽  
Wei Huang ◽  
Yong Tang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Early Stage ◽  
Learning Ability ◽  
Middle Aged ◽  
Protein Levels ◽  
Spine Pathology ◽  
The Impact

Background: Studies have suggested that cognitive impairment in Alzheimer’s disease (AD) is associated with dendritic spine loss, especially in the hippocampus. Fluoxetine (FLX) has been shown to improve cognition in the early stage of AD and to be associated with diminishing synapse degeneration in the hippocampus. However, little is known about whether FLX affects the pathogenesis of AD in the middle-tolate stage and whether its effects are correlated with the amelioration of hippocampal dendritic dysfunction. Previously, it has been observed that FLX improves the spatial learning ability of middleaged APP/PS1 mice. Objective: In the present study, we further characterized the impact of FLX on dendritic spines in the hippocampus of middle-aged APP/PS1 mice. Results: It has been found that the numbers of dendritic spines in dentate gyrus (DG), CA1 and CA2/3 of hippocampus were significantly increased by FLX. Meanwhile, FLX effectively attenuated hyperphosphorylation of tau at Ser396 and elevated protein levels of postsynaptic density 95 (PSD-95) and synapsin-1 (SYN-1) in the hippocampus. Conclusion: These results indicated that the enhanced learning ability observed in FLX-treated middle-aged APP/PS1 mice might be associated with remarkable mitigation of hippocampal dendritic spine pathology by FLX and suggested that FLX might be explored as a new strategy for therapy of AD in the middle-to-late stage.

Neuroprotective Role of Diosgenin, A NGF Stimulator, Against Aβ (1–42) Induced Neurotoxicity in Animal Model of Alzheimer’s Disease

2021 ◽  
Author(s):  
Swati Som ◽  
Justin Antony ◽  
Palanisamy Dhanabal ◽  
Ponnusankar Sivasankaran
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Molecular Mechanisms ◽  
Protective Action ◽  
Amyloid Β ◽  
Spatial Learning And Memory ◽  
Avoidance Task ◽  
Model Of Alzheimer’S Disease

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.

Development and Regulation of Dendritic Spine Synapses

Physiology ◽  
2006 ◽  
Vol 21 (1) ◽  
pp. 38-47 ◽  
Author(s):  
Barbara Calabrese ◽  
Margaret S. Wilson ◽  
Shelley Halpain
Keyword(s):  
Synaptic Transmission ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Excitatory Synapses ◽  
Dense Array ◽  
Complex Dynamic ◽  
Neuronal Dendrites ◽  
Spine Abnormalities ◽  
Dynamic Structures ◽  
The Brain

Dendritic spines are small protrusions from neuronal dendrites that form the postsynaptic component of most excitatory synapses in the brain. They play critical roles in synaptic transmission and plasticity. Recent advances in imaging and molecular technologies reveal that spines are complex, dynamic structures that contain a dense array of cytoskeletal, transmembrane, and scaffolding molecules. Several neurological and psychiatric disorders exhibit dendritic spine abnormalities.

scholarly journals Intraneuronal APP and extracellular Aβ independently cause dendritic spine pathology in transgenic mouse models of Alzheimer’s disease

2015 ◽  
Vol 129 (6) ◽  
pp. 909-920 ◽  
Author(s):  
Chengyu Zou ◽  
Elena Montagna ◽  
Yuan Shi ◽  
Finn Peters ◽  
Lidia Blazquez-Llorca ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mouse ◽  
Mouse Models ◽  
Dendritic Spine ◽  
Transgenic Mouse Models ◽  
Spine Pathology

scholarly journals Analyzing dendritic spine pathology in Alzheimer’s disease: problems and opportunities

2015 ◽  
Vol 130 (1) ◽  
pp. 1-19 ◽  
Author(s):  
Mario M. Dorostkar ◽  
Chengyu Zou ◽  
Lidia Blazquez-Llorca ◽  
Jochen Herms
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dendritic Spine ◽  
Spine Pathology

scholarly journals Dendritic spines are lost in clusters in Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mite Mijalkov ◽  
Giovanni Volpe ◽  
Isabel Fernaud-Espinosa ◽  
Javier DeFelipe ◽  
Joana B. Pereira ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dendritic Spines ◽  
Neurodegenerative Disorder ◽  
Pyramidal Cells ◽  
Memory Deficits ◽  
Memory Storage ◽  
Excitatory Synapses ◽  
Tau Pathology ◽  
Insight Into

AbstractAlzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by a deterioration of neuronal connectivity. The pathological accumulation of tau in neurons is one of the hallmarks of AD and has been connected to the loss of dendritic spines of pyramidal cells, which are the major targets of cortical excitatory synapses and key elements in memory storage. However, the detailed mechanisms underlying the loss of dendritic spines in individuals with AD are still unclear. Here, we used graph-theory approaches to compare the distribution of dendritic spines from neurons with and without tau pathology of AD individuals. We found that the presence of tau pathology determines the loss of dendritic spines in clusters, ruling out alternative models where spine loss occurs at random locations. Since memory storage has been associated with synaptic clusters, the present results provide a new insight into the mechanisms by which tau drives synaptic damage in AD, paving the way to memory deficits through alterations of spine organization.

scholarly journals Dendritic spines are lost in clusters in patients with Alzheimer’s disease

2020 ◽  
Author(s):  
Mite Mijalkov ◽  
Giovanni Volpe ◽  
Isabel Fernaud-Espinosa ◽  
Javier DeFelipe ◽  
Joana B. Pereira ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dendritic Spines ◽  
Neurodegenerative Disorder ◽  
Pyramidal Cells ◽  
Memory Deficits ◽  
Memory Storage ◽  
Excitatory Synapses ◽  
Tau Pathology ◽  
Insight Into

SUMMARYAlzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by a deterioration of neuronal connectivity. The pathological accumulation of tau protein in neurons is one of the hallmarks of AD and has been connected to the loss of dendritic spines of pyramidal cells, which are the major targets of cortical excitatory synapses and key elements in memory storage. However, the detailed mechanisms underlying the loss of dendritic spines in patients with AD are still unclear. Here, comparing dendrites with and without tau pathology of AD patients, we show that the presence of tau pathology determines the loss of dendritic spines in blocks, ruling out alternative models where spine loss occurs randomly. Since memory storage has been associated with synaptic clusters, the present results provide a new insight into the mechanisms by which tau drives synaptic damage in AD, paving the way to memory deficits by altering spine organization.

scholarly journals Neuroprotective Effects of Tripeptides—Epigenetic Regulators in Mouse Model of Alzheimer’s Disease

2021 ◽  
Vol 14 (6) ◽  
pp. 515
Author(s):  
Vladimir Khavinson ◽  
Anastasiia Ilina ◽  
Nina Kraskovskaya ◽  
Natalia Linkova ◽  
Nina Kolchina ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Dna Sequences ◽  
Dendritic Spine ◽  
Molecular Mechanisms ◽  
Neuroprotective Effect ◽  
Intraperitoneal Administration ◽  
Neuroprotective Effects ◽  
Model Of Alzheimer’S Disease

KED and EDR peptides prevent dendritic spines loss in amyloid synaptotoxicity in in vitro model of Alzheimer’s disease (AD). The objective of this paper was to study epigenetic mechanisms of EDR and KED peptides’ neuroprotective effects on neuroplasticity and dendritic spine morphology in an AD mouse model. Daily intraperitoneal administration of the KED peptide in 5xFAD mice from 2 to 4 months of age at a concentration of 400 μg/kg tended to increase neuroplasticity. KED and EDR peptides prevented dendritic spine loss in 5xFAD-M mice. Their action’s possible molecular mechanisms were investigated by molecular modeling and docking of peptides in dsDNA, containing all possible combinations of hexanucleotide sequences. Similar DNA sequences were found in the lowest-energy complexes of the studied peptides with DNA in the classical B-form. EDR peptide has binding sites in the promoter region of CASP3, NES, GAP43, APOE, SOD2, PPARA, PPARG, GDX1 genes. Protein products of these genes are involved in AD pathogenesis. The neuroprotective effect of EDR and KED peptides in AD can be defined by their ability to prevent dendritic spine elimination and neuroplasticity impairments at the molecular epigenetic level.

Dynamic Microtubules in Alzheimer’s Disease: Association with Dendritic Spine Pathology

2018 ◽  
Vol 83 (9) ◽  
pp. 1068-1074 ◽  
Author(s):  
E. I. Pchitskaya ◽  
V. A. Zhemkov ◽  
I. B. Bezprozvanny
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dendritic Spine ◽  
Disease Association ◽  
Spine Pathology

Dendritic Spines: Mediators of Cognitive Resilience in Aging and Alzheimer’s Disease

2020 ◽  
pp. 107385842094596 ◽  
Author(s):  
Courtney K. Walker ◽  
Jeremy H. Herskowitz
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Basic Structure ◽  
Spine Density ◽  
The Face ◽  
Plausible Mechanism ◽  
And Function ◽  
Spine Plasticity

Cognitive resilience is often defined as the ability to remain cognitively normal in the face of insults to the brain. These insults can include disease pathology, such as plaques and tangles associated with Alzheimer’s disease, stroke, traumatic brain injury, or other lesions. Factors such as physical or mental activity and genetics may contribute to cognitive resilience, but the neurobiological underpinnings remain ill-defined. Emerging evidence suggests that dendritic spine structural plasticity is one plausible mechanism. In this review, we highlight the basic structure and function of dendritic spines and discuss how spine density and morphology change in aging and Alzheimer’s disease. We note evidence that spine plasticity mediates resilience to stress, and we tackle dendritic spines in the context of cognitive resilience to Alzheimer’s disease. Finally, we examine how lifestyle and genetic factors may influence dendritic spine plasticity to promote cognitive resilience before discussing evidence for actin regulatory kinases as therapeutic targets for Alzheimer’s disease.

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