LIVIVO - Search results -

Search results

Result 1 - 10 of total 22

Search options

Article ; Online: Shifting paradigms: The central role of microglia in Alzheimer's disease.

Schwabe, Tina / Srinivasan, Karpagam / Rhinn, Herve

2020 Volume 143, Page(s) 104962

Abstract: Recent human genetic studies have challenged long standing hypotheses about the chain of events in Alzheimer's disease (AD), as the identification of genetic risk factors in microglial genes supports a causative role for microglia in the disease. ... ...

Abstract	Recent human genetic studies have challenged long standing hypotheses about the chain of events in Alzheimer's disease (AD), as the identification of genetic risk factors in microglial genes supports a causative role for microglia in the disease. Parallel transcriptome and histology studies at the single-cell level revealed a rich palette of microglial states affected by disease status and genetic risk factors. Taken together, those findings support microglia dysfunction as a central mechanism in AD etiology and thus the therapeutic potential of modulating microglial activity for AD treatment. Here we review how human genetic studies discovered microglial AD risk genes, such as TREM2, CD33, MS4A and APOE, and how experimental studies are beginning to decipher the cellular functions of some of these genes. Our review also focuses on recent transcriptomic studies of human microglia from postmortem tissue to critically assess areas of similarity and dissimilarity between human and mouse models currently in use in order to better understand the biology of innate immunity in AD.
MeSH term(s)	Alzheimer Disease/genetics ; Alzheimer Disease/pathology ; Animals ; Brain/pathology ; Genetic Predisposition to Disease ; Humans ; Microglia/pathology
Language	English
Publishing date	2020-06-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1211786-9
ISSN	1095-953X ; 0969-9961
ISSN (online)	1095-953X
ISSN	0969-9961
DOI	10.1016/j.nbd.2020.104962
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4444: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Alzheimer's Patient Microglia Exhibit Enhanced Aging and Unique Transcriptional Activation.

Srinivasan, Karpagam / Friedman, Brad A / Etxeberria, Ainhoa / Huntley, Melanie A / van der Brug, Marcel P / Foreman, Oded / Paw, Jonathan S / Modrusan, Zora / Beach, Thomas G / Serrano, Geidy E / Hansen, David V

Cell reports

2020 Volume 31, Issue 13, Page(s) 107843

Abstract: Damage-associated microglia (DAM) profiles observed in Alzheimer's disease (AD)-related mouse models reflect an activation state that could modulate AD risk or progression. To learn whether human AD microglia (HAM) display a similar profile, we develop a ...

Abstract	Damage-associated microglia (DAM) profiles observed in Alzheimer's disease (AD)-related mouse models reflect an activation state that could modulate AD risk or progression. To learn whether human AD microglia (HAM) display a similar profile, we develop a method for purifying cell types from frozen cerebrocortical tissues for RNA-seq analysis, allowing better transcriptome coverage than typical single-nucleus RNA-seq approaches. The HAM profile we observe bears little resemblance to the DAM profile. Instead, HAM display an enhanced human aging profile, in addition to other disease-related changes such as APOE upregulation. Analyses of whole-tissue RNA-seq and single-cell/nucleus RNA-seq datasets corroborate our findings and suggest that the lack of DAM response in human microglia occurs specifically in AD tissues, not other neurodegenerative settings. These results, which can be browsed at http://research-pub.gene.com/BrainMyeloidLandscape, provide a genome-wide picture of microglial activation in human AD and highlight considerable differences between mouse models and human disease.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/genetics ; Alzheimer Disease/pathology ; Animals ; Cellular Senescence/genetics ; Databases, Genetic ; Female ; Frontal Lobe/pathology ; Frozen Sections ; Gene Expression Profiling ; Genetic Predisposition to Disease ; Heterografts ; Humans ; Male ; Mice ; Microglia/metabolism ; Microglia/pathology ; Monocytes/metabolism ; Multiple Sclerosis/pathology ; Phenotype ; Reproducibility of Results ; Risk Factors ; Temporal Lobe/pathology ; Transcriptional Activation/genetics
Language	English
Publishing date	2020-06-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2020.107843
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Genome-Wide Analysis of Differential Gene Expression and Splicing in Excitatory Neurons and Interneuron Subtypes.

Huntley, Melanie A / Srinivasan, Karpagam / Friedman, Brad A / Wang, Tzu-Ming / Yee, Ada X / Wang, Yuanyuan / Kaminker, Josh S / Sheng, Morgan / Hansen, David V / Hanson, Jesse E

The Journal of neuroscience : the official journal of the Society for Neuroscience

2019 Volume 40, Issue 5, Page(s) 958–973

Abstract: Cortical circuit activity is shaped by the parvalbumin (PV) and somatostatin (SST) interneurons that inhibit principal excitatory (EXC) neurons and the vasoactive intestinal peptide (VIP) interneurons that suppress activation of other interneurons. To ... ...

Abstract	Cortical circuit activity is shaped by the parvalbumin (PV) and somatostatin (SST) interneurons that inhibit principal excitatory (EXC) neurons and the vasoactive intestinal peptide (VIP) interneurons that suppress activation of other interneurons. To understand the molecular-genetic basis of functional specialization and identify potential drug targets specific to each neuron subtype, we performed a genome wide assessment of both gene expression and splicing across EXC, PV, SST and VIP neurons from male and female mouse brains. These results reveal numerous examples where neuron subtype-specific gene expression, as well as splice-isoform usage, can explain functional differences between neuron subtypes, including in presynaptic plasticity, postsynaptic receptor function, and synaptic connectivity specification. We provide a searchable web resource for exploring differential mRNA expression and splice form usage between excitatory, PV, SST, and VIP neurons (http://research-pub.gene.com/NeuronSubtypeTranscriptomes). This resource, combining a unique new dataset and novel application of analysis methods to multiple relevant datasets, identifies numerous potential drug targets for manipulating circuit function, reveals neuron subtype-specific roles for disease-linked genes, and is useful for understanding gene expression changes observed in human patient brains.
MeSH term(s)	Animals ; Cells, Cultured ; Cerebral Cortex/metabolism ; Female ; Hippocampus/metabolism ; Interneurons/metabolism ; Male ; Mice, Transgenic ; Neurons/metabolism ; Parvalbumins/metabolism ; RNA, Messenger/metabolism ; Somatostatin/metabolism ; Transcriptome ; Vasoactive Intestinal Peptide/metabolism
Chemical Substances	Parvalbumins ; RNA, Messenger ; Vasoactive Intestinal Peptide (37221-79-7) ; Somatostatin (51110-01-1)
Language	English
Publishing date	2019-12-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.1615-19.2019
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1668: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: The rho GTPase Rac1 is required for proliferation and survival of progenitors in the developing forebrain.

Leone, Dino P / Srinivasan, Karpagam / Brakebusch, Cord / McConnell, Susan K

Developmental neurobiology

2010 Volume 70, Issue 9, Page(s) 659–678

Abstract: Progenitor cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing forebrain give rise to neurons and glial cells, and are characterized by distinct morphologies and proliferative behaviors. The mechanisms that distinguish VZ ... ...

Abstract	Progenitor cells in the ventricular zone (VZ) and subventricular zone (SVZ) of the developing forebrain give rise to neurons and glial cells, and are characterized by distinct morphologies and proliferative behaviors. The mechanisms that distinguish VZ and SVZ progenitors are not well understood, although the homeodomain transcription factor Cux2 and Cyclin D2, a core component of the cell cycle machinery, are specifically involved in controlling SVZ cell proliferation. Rho GTPases have been implicated in regulating the proliferation, differentiation, and migration of many cell types, and one family member, Cdc42, affects the polarity and proliferation of radial glial cells in the VZ. Here, we show that another family member, Rac1, is required for the normal proliferation and differentiation of SVZ progenitors and for survival of both VZ and SVZ progenitors. A forebrain-specific loss of Rac1 leads to an SVZ-specific reduction in proliferation, a concomitant increase in cell cycle exit, and premature differentiation. In Rac1 mutants, the SVZ and VZ can no longer be delineated, but rather fuse to become a single compact zone of intermingled cells. Cyclin D2 expression, which is normally expressed by both VZ and SVZ progenitors, is reduced in Rac1 mutants, suggesting that the mutant cells differentiate precociously. Rac1-deficient mice can still generate SVZ-derived upper layer neurons, indicating that Rac1 is not required for the acquisition of upper layer neuronal fates, but instead is needed for the normal regulation of proliferation by progenitor cells in the SVZ.
MeSH term(s)	Animals ; Apoptosis/physiology ; Cell Differentiation/physiology ; Cell Movement/physiology ; Cell Proliferation ; Cell Survival/physiology ; Cerebral Cortex/embryology ; Cerebral Cortex/pathology ; Cerebral Cortex/physiology ; Cyclin D1/metabolism ; Cyclin D2/metabolism ; Immunohistochemistry ; In Situ Hybridization ; Mice ; Mice, Knockout ; Neurogenesis/physiology ; Neurons/physiology ; Neuropeptides/deficiency ; Neuropeptides/genetics ; Neuropeptides/metabolism ; Prosencephalon/embryology ; Prosencephalon/pathology ; Prosencephalon/physiology ; Stem Cell Niche/embryology ; Stem Cell Niche/pathology ; Stem Cell Niche/physiology ; Stem Cells/physiology ; rac GTP-Binding Proteins/deficiency ; rac GTP-Binding Proteins/genetics ; rac GTP-Binding Proteins/metabolism ; rac1 GTP-Binding Protein
Chemical Substances	Ccnd1 protein, mouse ; Ccnd2 protein, mouse ; Cyclin D2 ; Neuropeptides ; Rac1 protein, mouse ; Cyclin D1 (136601-57-5) ; rac GTP-Binding Proteins (EC 3.6.5.2) ; rac1 GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2010-05-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2256184-5
ISSN	1932-846X ; 1097-4695 ; 1932-8451 ; 0022-3034
ISSN (online)	1932-846X ; 1097-4695
ISSN	1932-8451 ; 0022-3034
DOI	10.1002/dneu.20804
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 853: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Endocytosis regulates cell soma translocation and the distribution of adhesion proteins in migrating neurons.

Shieh, Jennifer C / Schaar, Bruce T / Srinivasan, Karpagam / Brodsky, Frances M / McConnell, Susan K

PloS one

2011 Volume 6, Issue 3, Page(s) e17802

Abstract: Newborn neurons migrate from their birthplace to their final location to form a properly functioning nervous system. During these movements, young neurons must attach and subsequently detach from their substrate to facilitate migration, but little is ... ...

Abstract	Newborn neurons migrate from their birthplace to their final location to form a properly functioning nervous system. During these movements, young neurons must attach and subsequently detach from their substrate to facilitate migration, but little is known about the mechanisms cells use to release their attachments. We show that the machinery for clathrin-mediated endocytosis is positioned to regulate the distribution of adhesion proteins in a subcellular region just proximal to the neuronal cell body. Inhibiting clathrin or dynamin function impedes the movement of migrating neurons both in vitro and in vivo. Inhibiting dynamin function in vitro shifts the distribution of adhesion proteins to the rear of the cell. These results suggest that endocytosis may play a critical role in regulating substrate detachment to enable cell body translocation in migrating neurons.
MeSH term(s)	Cell Adhesion ; Clathrin/physiology ; Dynamins/physiology ; Electroporation ; Endocytosis ; Humans ; Immunohistochemistry ; Microscopy, Electron ; Neurons/metabolism
Chemical Substances	Clathrin ; Dynamins (EC 3.6.5.5)
Language	English
Publishing date	2011-03-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0017802
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Trem2 Deletion Reduces Late-Stage Amyloid Plaque Accumulation, Elevates the Aβ42:Aβ40 Ratio, and Exacerbates Axonal Dystrophy and Dendritic Spine Loss in the PS2APP Alzheimer's Mouse Model.

The Journal of neuroscience : the official journal of the Society for Neuroscience

2020 Volume 40, Issue 9, Page(s) 1956–1974

Abstract: ... ...

Abstract	TREM2
MeSH term(s)	Alzheimer Disease/genetics ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/metabolism ; Amyloid beta-Protein Precursor/genetics ; Animals ; Axons/pathology ; Dendritic Spines/pathology ; Female ; Male ; Membrane Glycoproteins/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microglia/pathology ; Neurites/pathology ; Neurofilament Proteins/cerebrospinal fluid ; Peptide Fragments/metabolism ; Plaque, Amyloid/genetics ; Plaque, Amyloid/pathology ; Receptors, Immunologic/genetics ; Trefoil Factor-1/metabolism
Chemical Substances	APP protein, mouse ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; Membrane Glycoproteins ; Neurofilament Proteins ; Peptide Fragments ; Receptors, Immunologic ; Tff1 protein, mouse ; Trefoil Factor-1 ; Trem2 protein, mouse ; amyloid beta-protein (1-40) ; amyloid beta-protein (1-42)
Language	English
Publishing date	2020-01-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.1871-19.2019
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1668: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Progranulin deficiency causes impairment of autophagy and TDP-43 accumulation.

Chang, Michael C / Srinivasan, Karpagam / Friedman, Brad A / Suto, Eric / Modrusan, Zora / Lee, Wyne P / Kaminker, Joshua S / Hansen, David V / Sheng, Morgan

The Journal of experimental medicine

2017 Volume 214, Issue 9, Page(s) 2611–2628

Abstract: Loss-of-function mutations ... ...

Abstract	Loss-of-function mutations in
MeSH term(s)	Animals ; Autophagy/physiology ; DNA-Binding Proteins/metabolism ; Intercellular Signaling Peptides and Proteins/deficiency ; Listeria monocytogenes/immunology ; Listeriosis/immunology ; Macrophages/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microglia/metabolism ; Transcriptome
Chemical Substances	DNA-Binding Proteins ; Grn protein, mouse ; Intercellular Signaling Peptides and Proteins ; TDP-43 protein, mouse
Language	English
Publishing date	2017-08-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20160999
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ua VI Zs.107: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 45: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Diverse Brain Myeloid Expression Profiles Reveal Distinct Microglial Activation States and Aspects of Alzheimer's Disease Not Evident in Mouse Models.

Friedman, Brad A / Srinivasan, Karpagam / Ayalon, Gai / Meilandt, William J / Lin, Han / Huntley, Melanie A / Cao, Yi / Lee, Seung-Hye / Haddick, Patrick C G / Ngu, Hai / Modrusan, Zora / Larson, Jessica L / Kaminker, Joshua S / van der Brug, Marcel P / Hansen, David V

Cell reports

2018 Volume 22, Issue 3, Page(s) 832–847

Abstract: Microglia, the CNS-resident immune cells, play important roles in disease, but the spectrum of their possible activation states is not well understood. We derived co-regulated gene modules from transcriptional profiles of CNS myeloid cells of diverse ... ...

Abstract	Microglia, the CNS-resident immune cells, play important roles in disease, but the spectrum of their possible activation states is not well understood. We derived co-regulated gene modules from transcriptional profiles of CNS myeloid cells of diverse mouse models, including new tauopathy model datasets. Using these modules to interpret single-cell data from an Alzheimer's disease (AD) model, we identified microglial subsets-distinct from previously reported "disease-associated microglia"-expressing interferon-related or proliferation modules. We then analyzed whole-tissue RNA profiles from human neurodegenerative diseases, including a new AD dataset. Correcting for altered cellular composition of AD tissue, we observed elevated expression of the neurodegeneration-related modules, but also modules not implicated using expression profiles from mouse models alone. We provide a searchable, interactive database for exploring gene expression in all these datasets (http://research-pub.gene.com/BrainMyeloidLandscape). Understanding the dimensions of CNS myeloid cell activation in human disease may reveal opportunities for therapeutic intervention.
MeSH term(s)	Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Animals ; Brain/metabolism ; Disease Models, Animal ; Humans ; Mice ; Microglia/metabolism
Language	English
Publishing date	2018-01-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2017.12.066
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Changes in the Synaptic Proteome in Tauopathy and Rescue of Tau-Induced Synapse Loss by C1q Antibodies.

Dejanovic, Borislav / Huntley, Melanie A / De Mazière, Ann / Meilandt, William J / Wu, Tiffany / Srinivasan, Karpagam / Jiang, Zhiyu / Gandham, Vineela / Friedman, Brad A / Ngu, Hai / Foreman, Oded / Carano, Richard A D / Chih, Ben / Klumperman, Judith / Bakalarski, Corey / Hanson, Jesse E / Sheng, Morgan

Neuron

2018 Volume 100, Issue 6, Page(s) 1322–1336.e7

Abstract: Synapse loss and Tau pathology are hallmarks of Alzheimer's disease (AD) and other tauopathies, but how Tau pathology causes synapse loss is unclear. We used unbiased proteomic analysis of postsynaptic densities (PSDs) in Tau-P301S transgenic mice to ... ...

Abstract	Synapse loss and Tau pathology are hallmarks of Alzheimer's disease (AD) and other tauopathies, but how Tau pathology causes synapse loss is unclear. We used unbiased proteomic analysis of postsynaptic densities (PSDs) in Tau-P301S transgenic mice to identify Tau-dependent alterations in synapses prior to overt neurodegeneration. Multiple proteins and pathways were altered in Tau-P301S PSDs, including depletion of a set of GTPase-regulatory proteins that leads to actin cytoskeletal defects and loss of dendritic spines. Furthermore, we found striking accumulation of complement C1q in the PSDs of Tau-P301S mice and AD patients. At synapses, C1q decorated perisynaptic membranes, accumulated in correlation with phospho-Tau, and was associated with augmented microglial engulfment of synapses and decline of synapse density. A C1q-blocking antibody inhibited microglial synapse removal in cultured neurons and in Tau-P301S mice, rescuing synapse density. Thus, inhibiting complement-mediated synapse removal by microglia could be a potential therapeutic target for Tau-associated neurodegeneration.
MeSH term(s)	Amyloid beta-Protein Precursor/genetics ; Amyloid beta-Protein Precursor/metabolism ; Animals ; Animals, Newborn ; Antibodies/therapeutic use ; Cell Differentiation ; Cells, Cultured ; Complement C1q/immunology ; Complement C1q/metabolism ; Complement C1q/ultrastructure ; Embryo, Mammalian ; Female ; Humans ; Induced Pluripotent Stem Cells/drug effects ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mutation/genetics ; Post-Synaptic Density/metabolism ; Post-Synaptic Density/pathology ; Post-Synaptic Density/ultrastructure ; Presenilin-2/genetics ; Presenilin-2/metabolism ; Prion Proteins/genetics ; Prion Proteins/metabolism ; Proteome/metabolism ; Rats ; Synapses/drug effects ; Synapses/metabolism ; Synapses/ultrastructure ; Tauopathies/diagnostic imaging ; Tauopathies/drug therapy ; Tauopathies/genetics ; Tauopathies/pathology ; tau Proteins/genetics ; tau Proteins/metabolism
Chemical Substances	Amyloid beta-Protein Precursor ; Antibodies ; PRNP protein, human ; Presenilin-2 ; Prion Proteins ; Proteome ; tau Proteins ; Complement C1q (80295-33-6)
Language	English
Publishing date	2018-11-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	808167-0
ISSN	1097-4199 ; 0896-6273
ISSN (online)	1097-4199
ISSN	0896-6273
DOI	10.1016/j.neuron.2018.10.014
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 2496: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 92: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Interfering with the Chronic Immune Response Rescues Chronic Degeneration After Traumatic Brain Injury.

Ertürk, Ali / Mentz, Susanne / Stout, Erik E / Hedehus, Maj / Dominguez, Sara L / Neumaier, Lisa / Krammer, Franziska / Llovera, Gemma / Srinivasan, Karpagam / Hansen, David V / Liesz, Arthur / Scearce-Levie, Kimberly A / Sheng, Morgan

The Journal of neuroscience : the official journal of the Society for Neuroscience

2016 Volume 36, Issue 38, Page(s) 9962–9975

Abstract: Unlabelled: After traumatic brain injury (TBI), neurons surviving the initial insult can undergo chronic (secondary) degeneration via poorly understood mechanisms, resulting in long-term cognitive impairment. Although a neuroinflammatory response is ... ...

Abstract	Unlabelled: After traumatic brain injury (TBI), neurons surviving the initial insult can undergo chronic (secondary) degeneration via poorly understood mechanisms, resulting in long-term cognitive impairment. Although a neuroinflammatory response is promptly activated after TBI, it is unknown whether it has a significant role in chronic phases of TBI (>1 year after injury). Using a closed-head injury model of TBI in mice, we showed by MRI scans that TBI caused substantial degeneration at the lesion site within a few weeks and these did not expand significantly thereafter. However, chronic alterations in neurons were observed, with reduced dendritic spine density lasting >1 year after injury. In parallel, we found a long-lasting inflammatory response throughout the entire brain. Deletion of one allele of CX3CR1, a chemokine receptor, limited infiltration of peripheral immune cells and largely prevented the chronic degeneration of the injured brain and provided a better functional recovery in female, but not male, mice. Therefore, targeting persistent neuroinflammation presents a new therapeutic option to reduce chronic neurodegeneration. Significance statement: Traumatic brain injury (TBI) often causes chronic neurological problems including epilepsy, neuropsychiatric disorders, and dementia through unknown mechanisms. Our study demonstrates that inflammatory cells invading the brain lead to secondary brain damage. Sex-specific amelioration of chronic neuroinflammation rescues the brain degeneration and results in improved motor functions. Therefore, this study pinpoints an effective therapeutic approach to preventing secondary complications after TBI.
MeSH term(s)	Animals ; Brain/pathology ; Brain Injuries, Traumatic/complications ; CX3C Chemokine Receptor 1 ; Calcium-Binding Proteins/metabolism ; Chronic Disease ; Dendritic Spines/immunology ; Dendritic Spines/pathology ; Dendritic Spines/ultrastructure ; Disease Models, Animal ; Exploratory Behavior/physiology ; Female ; Inflammation/etiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microfilament Proteins/metabolism ; Motor Activity ; Nerve Degeneration/diagnostic imaging ; Nerve Degeneration/etiology ; Nerve Degeneration/pathology ; Neurons/metabolism ; Neurons/pathology ; Psychomotor Performance/physiology ; Receptors, Chemokine/genetics ; Receptors, Chemokine/metabolism ; Recovery of Function/physiology ; Time Factors
Chemical Substances	Aif1 protein, mouse ; CX3C Chemokine Receptor 1 ; Calcium-Binding Proteins ; Cx3cr1 protein, mouse ; Microfilament Proteins ; Receptors, Chemokine
Language	English
Publishing date	2016-09-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.1898-15.2016
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1668: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito