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Neuroscience Letters Aug 2015Schizophrenia is a chronic illness affecting approximately 0.5-1% of the world's population. The etiology of schizophrenia is complex, including multiple genes, and... (Review)
Review
Schizophrenia is a chronic illness affecting approximately 0.5-1% of the world's population. The etiology of schizophrenia is complex, including multiple genes, and contributing environmental effects that adversely impact neurodevelopment. Nevertheless, a final common result, present in many subjects with schizophrenia, is impairment of pyramidal neuron dendritic morphology in multiple regions of the cerebral cortex. In this review, we summarize the evidence of reduced dendritic spine density and other dendritic abnormalities in schizophrenia, evaluate current data that informs the neurodevelopment timing of these impairments, and discuss what is known about possible upstream sources of dendritic spine loss in this illness.
Topics: Age Factors; Animals; Brain; Dendritic Spines; Humans; Schizophrenia
PubMed: 25478958
DOI: 10.1016/j.neulet.2014.11.042 -
Neural Plasticity 2016
Topics: Animals; Dendritic Spines; Humans; Neuronal Plasticity
PubMed: 27127656
DOI: 10.1155/2016/2078121 -
Advances in Protein Chemistry and... 2022Dendritic spines are small protrusions stemming from the dendritic shaft that constitute the primary specialization for receiving and processing excitatory...
Dendritic spines are small protrusions stemming from the dendritic shaft that constitute the primary specialization for receiving and processing excitatory neurotransmission in brain synapses. The disruption of dendritic spine function in several neurological and neuropsychiatric diseases leads to severe information-processing deficits with impairments in neuronal connectivity and plasticity. Spine dysregulation is usually accompanied by morphological alterations to spine shape, size and/or number that may occur at early pathophysiological stages and not necessarily be reflected in clinical manifestations. Autism spectrum disorder (ASD) is one such group of diseases involving changes in neuronal connectivity and abnormal morphology of dendritic spines on postsynaptic neurons. These alterations at the subcellular level correlate with molecular changes in the spine proteome, with alterations in the copy number, topography, or in severe cases in the phenotype of the molecular components, predominantly of those proteins involved in spine recognition and adhesion, reflected in abnormally short lifetimes of the synapse and compensatory increases in synaptic connections. Since cholinergic neurotransmission participates in the regulation of cognitive function (attention, memory, learning processes, cognitive flexibility, social interactions) brain acetylcholine receptors are likely to play an important role in the dysfunctional synapses in ASD, either directly or indirectly via the modulatory functions exerted on other neurotransmitter receptor proteins and spine-resident proteins.
Topics: Autism Spectrum Disorder; Dendritic Spines; Humans; Neuronal Plasticity; Neurons; Proteome; Synapses
PubMed: 35034726
DOI: 10.1016/bs.apcsb.2021.09.003 -
Advances in Experimental Medicine and... 2017Drebrin is localized in actin-rich regions of neuronal and non-neuronal cells. In mature neurons, its localization is strictly restricted to the postsynaptic sites. In... (Review)
Review
Drebrin is localized in actin-rich regions of neuronal and non-neuronal cells. In mature neurons, its localization is strictly restricted to the postsynaptic sites. In order to understand the function of drebrin in cells, many studies have been performed to examine the effect of overexpression or knocking down of drebrin in various cell types, including neurons, myoblasts, kidney cells, and intestinal epithelial cells. In most cases alteration of cell shape and impairment or facilitation of actin-based activities of these cells were observed. Interestingly, overexpression of drebrin in matured neurons results in the alteration in dendritic spine morphology. Further studies have shown alteration in the localization of postsynaptic receptors and even changes in synaptic transmission caused by drebrin overexpression or depletion in neurons. These drebrin's effects are thought to come from drebrin's actin-cross-linking activity or competitive binding to actin against tropomyosin, fascin, and α-actinin. Furthermore, drebrin binds to various molecules, such as homer, EB3, and cell-cell junctional proteins, indicating that drebrin is a multifunctional cytoskeletal regulator.
Topics: Actins; Animals; Axons; Cell Movement; Cell Shape; Cytoskeleton; Dendrites; Dendritic Spines; Hippocampus; Neurons; Neuropeptides; Synapses; Synaptic Transmission
PubMed: 28865016
DOI: 10.1007/978-4-431-56550-5_6 -
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 -
Neuroscience Feb 2021Synapse or dendritic spine loss is the strongest correlate of cognitive decline in Alzheimer's disease (AD), and neurofibrillary tangles (NFTs), but not amyloid-β...
Synapse or dendritic spine loss is the strongest correlate of cognitive decline in Alzheimer's disease (AD), and neurofibrillary tangles (NFTs), but not amyloid-β plaques, associate more closely with transition to mild cognitive impairment. Yet, how dendritic spine architecture is affected by hyperphosphorylated tau is still an ongoing question. To address this, we combined cell and biochemical analyses of the Tau P301S mouse line (PS19). Individual pyramidal neurons in the hippocampus and medial prefrontal cortex (mPFC) were targeted for iontophoretic microinjection of fluorescent dye, followed by high-resolution confocal microscopy and 3D morphometry analysis. In the hippocampus, PS19 mice and non-transgenic (NTG) littermates displayed equivalent spine density at 6 and 9 months, but both genotypes exhibited age-related thin spine loss. PS19 mice exhibited significant increases in synaptic tau protein levels and mean dendritic spine head diameter with age. This suggests that CA1 pyramidal neurons in PS19 mice may undergo spine remodeling in response to tau accumulation and age. In the mPFC, spine density was similar among PS19 mice and NTG littermates at 6 and 9 months, but age-related reductions in synaptic tau levels were observed among PS19 mice. Collectively, these studies reveal brain region-specific changes in dendritic spine density and morphology in response to age and the presence of hyperphosphorylated tau in the PS19 mouse line.
Topics: Alzheimer Disease; Animals; Dendritic Spines; Disease Models, Animal; Hippocampus; Mice; Mice, Transgenic; Tauopathies; tau Proteins
PubMed: 33346120
DOI: 10.1016/j.neuroscience.2020.12.006 -
Acta Neuropathologica Jul 2015Synaptic failure is an immediate cause of cognitive decline and memory dysfunction in Alzheimer's disease. Dendritic spines are specialized structures on neuronal... (Review)
Review
Synaptic failure is an immediate cause of cognitive decline and memory dysfunction in Alzheimer's disease. Dendritic spines are specialized structures on neuronal processes, on which excitatory synaptic contacts take place and the loss of dendritic spines directly correlates with the loss of synaptic function. Dendritic spines are readily accessible for both in vitro and in vivo experiments and have, therefore, been studied in great detail in Alzheimer's disease mouse models. To date, a large number of different mechanisms have been proposed to cause dendritic spine dysfunction and loss in Alzheimer's disease. For instance, amyloid beta fibrils, diffusible oligomers or the intracellular accumulation of amyloid beta have been found to alter the function and structure of dendritic spines by distinct mechanisms. Furthermore, tau hyperphosphorylation and microglia activation, which are thought to be consequences of amyloidosis in Alzheimer's disease, may also contribute to spine loss. Lastly, genetic and therapeutic interventions employed to model the disease and elucidate its pathogenetic mechanisms in experimental animals may cause alterations of dendritic spines on their own. However, to date none of these mechanisms have been translated into successful therapeutic approaches for the human disease. Here, we critically review the most intensely studied mechanisms of spine loss in Alzheimer's disease as well as the possible pitfalls inherent in the animal models of such a complex neurodegenerative disorder.
Topics: Alzheimer Disease; Amyloid; Animals; Brain; Dendritic Spines; Humans
PubMed: 26063233
DOI: 10.1007/s00401-015-1449-5 -
Cells Sep 2021Dendritic spines are small, bulbous protrusions along neuronal dendrites where most of the excitatory synapses are located. Dendritic spine density in normal human brain... (Review)
Review
Dendritic spines are small, bulbous protrusions along neuronal dendrites where most of the excitatory synapses are located. Dendritic spine density in normal human brain increases rapidly before and after birth achieving the highest density around 2-8 years. Density decreases during adolescence, reaching a stable level in adulthood. The changes in dendritic spines are considered structural correlates for synaptic plasticity as well as the basis of experience-dependent remodeling of neuronal circuits. Alterations in spine density correspond to aberrant brain function observed in various neurodevelopmental and neuropsychiatric disorders. Dendritic spine initiation affects spine density. In this review, we discuss the importance of spine initiation in brain development, learning, and potential complications resulting from altered spine initiation in neurological diseases. Current literature shows that two Bin Amphiphysin Rvs (BAR) domain-containing proteins, MIM/Mtss1 and SrGAP3, are involved in spine initiation. We review existing literature and open databases to discuss whether other BAR-domain proteins could also take part in spine initiation. Finally, we discuss the potential molecular mechanisms on how BAR-domain proteins could regulate spine initiation.
Topics: Adaptor Proteins, Signal Transducing; Brain; Brain Diseases; Dendritic Spines; Humans; Learning; Nuclear Proteins; Protein Domains; Tumor Suppressor Proteins
PubMed: 34572042
DOI: 10.3390/cells10092392 -
Biomolecules Aug 2023Dendritic spines are actin-rich protrusions that receive a signal from the axon at the synapse. Remodeling of cytoskeletal actin is tightly connected to dendritic spine...
Dendritic spines are actin-rich protrusions that receive a signal from the axon at the synapse. Remodeling of cytoskeletal actin is tightly connected to dendritic spine morphology-mediated synaptic plasticity of the neuron. Remodeling of cytoskeletal actin is required for the formation, development, maturation, and reorganization of dendritic spines. Actin filaments are highly dynamic structures with slow-growing/pointed and fast-growing/barbed ends. Very few studies have been conducted on the role of pointed-end binding proteins in the regulation of dendritic spine morphology. In this study, we evaluated the role played by tropomodulin 2 (Tmod2)-a brain-specific isoform, on the dendritic spine re-organization. Tmod2 regulates actin nucleation and polymerization by binding to the pointed end via actin and tropomyosin (Tpm) binding sites. We studied the effects of Tmod2 overexpression in primary hippocampal neurons on spine morphology using confocal microscopy and image analysis. Tmod2 overexpression decreased the spine number and increased spine length. Destroying Tpm-binding ability increased the number of shaft synapses and thin spine motility. Eliminating the actin-binding abilities of Tmod2 increased the number of mushroom spines. Tpm-mediated pointed-end binding decreased F-actin depolymerization, which may positively affect spine stabilization; the nucleation ability of Tmod2 appeared to increase shaft synapses.
Topics: Actins; Dendritic Spines; Tropomodulin; Actin Cytoskeleton; Cytoskeleton
PubMed: 37627302
DOI: 10.3390/biom13081237 -
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