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Annual Review of Pathology May 2016Substantial progress has been made toward understanding the neuropathology, genetic origins, and epidemiology of neurodegenerative diseases, including Alzheimer's... (Review)
Review
Substantial progress has been made toward understanding the neuropathology, genetic origins, and epidemiology of neurodegenerative diseases, including Alzheimer's disease; tauopathies, such as frontotemporal dementia; α-synucleinopathies, such as Parkinson's disease or dementia with Lewy bodies; Huntington's disease; and amyotrophic lateral sclerosis with dementia, as well as prion diseases. Recent evidence has implicated dendritic spine dysfunction as an important substrate of the pathogenesis of dementia in these disorders. Dendritic spines are specialized structures, extending from the neuronal processes, on which excitatory synaptic contacts are formed, and the loss of dendritic spines correlates with the loss of synaptic function. We review the literature that has implicated direct or indirect structural alterations at dendritic spines in the pathogenesis of major neurodegenerative diseases, focusing on those that lead to dementias such as Alzheimer's, Parkinson's, and Huntington's diseases, as well as frontotemporal dementia and prion diseases. We stress the importance of in vivo studies in animal models.
Topics: Animals; Dendritic Spines; Humans; Neurodegenerative Diseases
PubMed: 26907528
DOI: 10.1146/annurev-pathol-012615-044216 -
Neural Plasticity 2012
Topics: Animals; Cognition; Dendritic Spines; Humans; Neuronal Plasticity
PubMed: 22690344
DOI: 10.1155/2012/875156 -
Cytoskeleton (Hoboken, N.J.) Sep 2016The majority of the postsynaptic terminals of excitatory synapses in the central nervous system exist on small bulbous structures on dendrites known as dendritic spines.... (Review)
Review
The majority of the postsynaptic terminals of excitatory synapses in the central nervous system exist on small bulbous structures on dendrites known as dendritic spines. The actin cytoskeleton is a structural element underlying the proper development and morphology of dendritic spines. Synaptic activity patterns rapidly change actin dynamics, leading to morphological changes in dendritic spines. In this mini-review, we will discuss recent findings on neuronal maturation and synaptic plasticity-induced changes in the dendritic spine actin cytoskeleton. We propose that actin dynamics in dendritic spines decrease through actin filament crosslinking during neuronal maturation. In long-term potentiation, we evaluate the model of fast breakdown of actin filaments through severing and rebuilding through polymerization and later stabilization through crosslinking. We will discuss the role of Ca(2+) in long-term depression, and suggest that actin filaments are dissolved through actin filament severing. © 2016 Wiley Periodicals, Inc.
Topics: Actin Cytoskeleton; Actins; Animals; Dendritic Spines; Humans; Long-Term Synaptic Depression; Models, Neurological
PubMed: 26849484
DOI: 10.1002/cm.21280 -
Movement Disorders : Official Journal... Jul 2018Parkinson's disease (PD) is a neurodegenerative disorder associated with the progressive loss of nigrostriatal dopaminergic neurons. Levodopa is the most effective... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disorder associated with the progressive loss of nigrostriatal dopaminergic neurons. Levodopa is the most effective treatment for the motor symptoms of PD. However, chronic oral levodopa treatment can lead to various motor and nonmotor complications because of nonphysiological pulsatile dopaminergic stimulation in the brain. Examinations of autopsy cases with PD have revealed a decreased number of dendritic spines of striatal neurons. Animal models of PD have revealed altered density and morphology of dendritic spines of neurons in various brain regions after dopaminergic denervation or dopaminergic denervation plus levodopa treatment, indicating altered synaptic transmission. Recent studies using rodent models have reported dendritic spine head enlargement in the caudate-putamen, nucleus accumbens, primary motor cortex, and prefrontal cortex in cases where chronic levodopa treatment following dopaminergic denervation induced dyskinesia-like abnormal involuntary movement. Hypertrophy of spines results from insertion of alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid receptors into the postsynaptic membrane. Such spine enlargement indicates hypersensitivity of the synapse to excitatory inputs and is compatible with a lack of depotentiation, which is an electrophysiological hallmark of levodopa-induced dyskinesia found in the corticostriatal synapses of dyskinetic animals and the motor cortex of dyskinetic PD patients. This synaptic plasticity may be one of the mechanisms underlying the priming of levodopa-induced complications such as levodopa-induced dyskinesia and dopamine dysregulation syndrome. Drugs that could potentially prevent spine enlargement, such as calcium channel blockers, N-methyl-D-aspartate receptor antagonists, alpha-amino-2,3-dihydro-5-methyl-3-oxo-4-isoxazolepropanoic acid receptor antagonists, and metabotropic glutamate receptor antagonists, are candidates for treatment of levodopa-induced complications in PD. © 2017 International Parkinson and Movement Disorder Society.
Topics: Animals; Antiparkinson Agents; Caudate Nucleus; Dendritic Spines; Dopaminergic Neurons; Dyskinesia, Drug-Induced; Humans; Levodopa; Parkinson Disease; Putamen
PubMed: 28880414
DOI: 10.1002/mds.27172 -
Neuroscience Oct 2013Abnormalities in dendritic spines have commonly been observed in brain specimens from epilepsy patients and animal models of epilepsy. However, the functional... (Review)
Review
Abnormalities in dendritic spines have commonly been observed in brain specimens from epilepsy patients and animal models of epilepsy. However, the functional implications and clinical consequences of this dendritic pathology for epilepsy are uncertain. Dendritic spine abnormalities may promote hyperexcitable circuits and seizures in some types of epilepsy, especially in specific genetic syndromes with documented dendritic pathology, but in these cases it is difficult to differentiate their effects on seizures versus other comorbidities, such as cognitive deficits and autism. In other situations, seizures themselves may cause damage to dendrites and dendritic spines and this seizure-induced brain injury may then contribute to progressive epileptogenesis, memory problems and other neurological deficits in epilepsy patients. The mechanistic basis of dendritic spine abnormalities in epilepsy has begun to be elucidated and suggests novel therapeutic strategies for treating epilepsy and its complications.
Topics: Animals; Dendritic Spines; Epilepsy; Humans
PubMed: 22522469
DOI: 10.1016/j.neuroscience.2012.03.048 -
Developmental Neurobiology Jul 2021Dendritic spines are small dendritic protrusions that harbor most excitatory synapses in the brain. The proper generation and maturation of dendritic spines are crucial... (Review)
Review
Dendritic spines are small dendritic protrusions that harbor most excitatory synapses in the brain. The proper generation and maturation of dendritic spines are crucial for the regulation of synaptic transmission and formation of neuronal circuits. Abnormalities in dendritic spine density and morphology are common pathologies in autism and schizophrenia. According to epidemiological studies, one risk factor for these neurodevelopmental disorders is maternal infection during pregnancy. This review discusses spine alterations in animal models of maternal immune activation in the context of neurodevelopmental disorders. We describe potential mechanisms that might be responsible for prenatal infection-induced changes in the dendritic spine phenotype and behavior in offspring.
Topics: Animals; Autistic Disorder; Dendritic Spines; Female; Neurodevelopmental Disorders; Neurons; Pregnancy; Synapses
PubMed: 33382515
DOI: 10.1002/dneu.22804 -
Current Opinion in Neurobiology Dec 2018Dendritic spines are the postsynaptic sites of most excitatory synapses in the cerebral cortex. Their morphology and density change throughout life, reflecting the... (Review)
Review
Dendritic spines are the postsynaptic sites of most excitatory synapses in the cerebral cortex. Their morphology and density change throughout life, reflecting the maturation and reorganization of excitatory circuits. The development of in vivo two-photon microscopy has enabled the monitoring of the same dendritic spines over time during different developmental periods. In this review we focus on recent in vivo imaging studies in rodents that have revealed cell type-specific and region-specific structural dynamics of dendritic spines. We also discuss how the contributions of local inhibitory neurons and long-distance excitatory and neuromodulatory inputs to the cortex influence dendritic spine development and dynamics. Such studies will facilitate our understanding of how environmental factors and experiences affect cortical synapse development.
Topics: Animals; Cerebral Cortex; Dendritic Spines; Excitatory Postsynaptic Potentials; Inhibitory Postsynaptic Potentials; Microscopy, Fluorescence, Multiphoton; Neuronal Plasticity; Signal Transduction
PubMed: 29936406
DOI: 10.1016/j.conb.2018.06.002 -
The Journal of General Physiology Aug 2022Dendritic spines act as biochemical computational units and must adapt their responses according to their activation history. Calcium influx acts as the first signaling...
Dendritic spines act as biochemical computational units and must adapt their responses according to their activation history. Calcium influx acts as the first signaling step during postsynaptic activation and is a determinant of synaptic weight change. Dendritic spines also come in a variety of sizes and shapes. To probe the relationship between calcium dynamics and spine morphology, we used a stochastic reaction-diffusion model of calcium dynamics in idealized and realistic geometries. We show that despite the stochastic nature of the various calcium channels, receptors, and pumps, spine size and shape can modulate calcium dynamics and subsequently synaptic weight updates in a deterministic manner. Through a series of exhaustive simulations and analyses, we found that the calcium dynamics and synaptic weight change depend on the volume-to-surface area of the spine. The relationships between calcium dynamics and spine morphology identified in idealized geometries also hold in realistic geometries, suggesting that there are geometrically determined deterministic relationships that may modulate synaptic weight change.
Topics: Calcium; Calcium Channels; Calcium Signaling; Dendritic Spines; Diffusion
PubMed: 35819365
DOI: 10.1085/jgp.202112980 -
Current Opinion in Neurobiology Apr 2009Formation, elimination and remodeling of excitatory synapses on dendritic spines represent a continuous process that shapes the organization of synaptic networks during... (Review)
Review
Formation, elimination and remodeling of excitatory synapses on dendritic spines represent a continuous process that shapes the organization of synaptic networks during development. The molecular mechanisms controlling dendritic spine formation and stabilization therefore critically determine the rules of network selectivity. Recent studies have identified new molecules, such as Ephrins and Telencephalin that regulate filopodia motility and their transformation into dendritic spines. Trans-synaptic signaling involving nitric oxide, protease, adhesion molecules and Rho GTPases further controls contact formation or the structural remodeling of spines and their stability. Evidence also suggests that activity and induction of plasticity participate to the selection of persistent spines. Together these new data provide a better understanding of the mechanisms, speed and steps leading to the establishment of a stable excitatory synapse.
Topics: Animals; Dendritic Spines; Models, Neurological; Neuronal Plasticity; Synapses
PubMed: 19523814
DOI: 10.1016/j.conb.2009.05.013 -
Trends in Neurosciences Aug 2008Changes in the structure and function of dendritic spines contribute to numerous physiological processes such as synaptic transmission and plasticity, as well as... (Review)
Review
Changes in the structure and function of dendritic spines contribute to numerous physiological processes such as synaptic transmission and plasticity, as well as behavior, including learning and memory. Moreover, altered dendritic spine morphogenesis and plasticity is an endophenotype of many neurodevelopmental and neuropsychiatric disorders. Hence, the molecular mechanisms that control spine plasticity and pathology have been under intense investigation over the past few years. A series of recent studies has improved our understanding of spine dynamics by establishing kalirin-7 as an important regulator of dendritic spine development as well as structural and functional plasticity, providing a model for the molecular control of structural plasticity and implicating kalirin-7 in synaptic pathology in several disorders including schizophrenia and Alzheimer's disease.
Topics: Animals; Cell Shape; Dendritic Spines; Guanine Nucleotide Exchange Factors; Humans; Nerve Tissue Proteins; Neurons; Protein Serine-Threonine Kinases; Signal Transduction
PubMed: 18597863
DOI: 10.1016/j.tins.2008.06.001