LIVIVO - Search results -

Search results

Result 1 - 10 of total 122

Search options

Article ; Online: Neuronal survival in the brain: neuron type-specific mechanisms.

Pfisterer, Ulrich / Khodosevich, Konstantin

2017 Volume 8, Issue 3, Page(s) e2643

Abstract: ... pro-survival signaling, different types of neurons possess a variety of 'neuron type-specific' pro ... responses depend on the type of neuron and region of the brain. Thus, in addition to some common neuronal ... focus on in vivo data to describe neuronal survival specifically in the brain, without extrapolating ...

Abstract	Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation. Furthermore, pro-survival factors and intracellular responses depend on the type of neuron and region of the brain. Thus, in addition to some common neuronal pro-survival signaling, different types of neurons possess a variety of 'neuron type-specific' pro-survival constituents that might help them to adapt for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various types of immature neurons. Importantly, we mainly focus on in vivo data to describe neuronal survival specifically in the brain, without extrapolating data obtained in the PNS or spinal cord, and thus emphasize the influence of the complex brain environment on neuronal survival during development.
MeSH term(s)	Animals ; Brain/physiology ; Cell Survival/physiology ; Humans ; Neurogenesis/physiology ; Neurons/physiology ; Signal Transduction/physiology
Language	English
Publishing date	2017-03-02
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/cddis.2017.64
Database	MEDical Literature Analysis and Retrieval System OnLINE

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.

Article ; Online: Temporal control of neuronal wiring.

Jain, S / Zipursky, S L

Seminars in cell & developmental biology

2022 Volume 142, Page(s) 81–90

Abstract: ... with high fidelity is critical for animal survival and behavior. Assembly of neuronal circuits is heavily ... to understanding the mechanisms underlying brain wiring, and will be critical for the development of in vitro ... Wiring an animal brain is a complex process involving a staggering number of cell-types born ...

Abstract	Wiring an animal brain is a complex process involving a staggering number of cell-types born at different times and locations in the developing brain. Incorporation of these cells into precise circuits with high fidelity is critical for animal survival and behavior. Assembly of neuronal circuits is heavily dependent upon proper timing of wiring programs, requiring neurons to express specific sets of genes (sometimes transiently) at the right time in development. While cell-type specificity of genetic programs regulating wiring has been studied in detail, mechanisms regulating proper timing and coordination of these programs across cell-types are only just beginning to emerge. In this review, we discuss some temporal regulators of wiring programs and how their activity is controlled over time and space. A common feature emerges from these temporal regulators - they are induced by cell-extrinsic cues and control transcription factors capable of regulating a highly cell-type specific set of target genes. Target specificity in these contexts comes from cell-type specific transcription factors. We propose that the spatiotemporal specificity of wiring programs is controlled by the combinatorial activity of temporal programs and cell-type specific transcription factors. Going forward, a better understanding of temporal regulators will be key to understanding the mechanisms underlying brain wiring, and will be critical for the development of in vitro models like brain organoids.
MeSH term(s)	Animals ; Neurons/physiology ; Brain/physiology ; Transcription Factors
Chemical Substances	Transcription Factors
Language	English
Publishing date	2022-05-26
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1312473-0
ISSN	1096-3634 ; 1084-9521
ISSN (online)	1096-3634
ISSN	1084-9521
DOI	10.1016/j.semcdb.2022.05.012
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 2918: 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

Details ▾

Article: Temporal control of neuronal wiring

Jain, S. / Zipursky, S.L.

Seminars in cell & developmental biology. 2022 May 16,

2022

Abstract	Wiring an animal brain is a complex process involving a staggering number of cell-types born at different times and locations in the developing brain. Incorporation of these cells into precise circuits with high fidelity is critical for animal survival and behavior. Assembly of neuronal circuits is heavily dependent upon proper timing of wiring programs, requiring neurons to express specific sets of genes (sometimes transiently) at the right time in development. While cell-type specificity of genetic programs regulating wiring has been studied in detail, mechanisms regulating proper timing and coordination of these programs across cell-types are only just beginning to emerge. In this review, we discuss some temporal regulators of wiring programs and how their activity is controlled over time and space. A common feature emerges from these temporal regulators - they are induced by cell-extrinsic cues and control transcription factors capable of regulating a highly cell-type specific set of target genes. Target specificity in these contexts comes from cell-type specific transcription factors. We propose that the spatiotemporal specificity of wiring programs is controlled by the combinatorial activity of temporal programs and cell-type specific transcription factors. Going forward, a better understanding of temporal regulators will be key to understanding the mechanisms underlying brain wiring, and will be critical for the development of in vitro models like brain organoids.
Keywords	animals ; brain ; cell specificity ; neurons ; organoids
Language	English
Dates of publication	2022-0516
Publishing place	Elsevier Ltd
Document type	Article
Note	Pre-press version
ZDB-ID	1312473-0
ISSN	1096-3634 ; 1084-9521
ISSN (online)	1096-3634
ISSN	1084-9521
DOI	10.1016/j.semcdb.2022.05.012
Database	NAL-Catalogue (AGRICOLA)

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 2918: 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

Details ▾

Article ; Online: Rb deficiency, neuronal survival and neurodegeneration: In search of the perfect mouse model.

Omais, Saad / El Atie, Yara E / Ghanem, Noël

Current research in neurobiology

2023 Volume 4, Page(s) 100074

Abstract: ... under inquiry especially when studying the role of Rb in neuronal survival. There is indeed evidence ... of age-specific, cell type-specific and region-specific effects following Rb KO in the embryonic and ... of this critical protein in regulating brain development during embryogenesis and beyond remains a major scientific ...

Abstract	Three decades following the introduction of the first Rb knockout (KO) mouse model, the role of this critical protein in regulating brain development during embryogenesis and beyond remains a major scientific interest. Rb is a tumor suppressor gene known as the master regulator of the G1/S checkpoint and control of cell cycle progression in stem and progenitor cells, but also their differentiated progeny. Here, we review the recent literature about the various Rb conditional Knockout (cKO) and inducible Knockout (iKO) models studied thus far, highlighting how findings should always be interpreted in light of the model and context under inquiry especially when studying the role of Rb in neuronal survival. There is indeed evidence of age-specific, cell type-specific and region-specific effects following Rb KO in the embryonic and the adult mouse brain. In terms of modeling neurodegenerative processes in human diseases, we discuss cell cycle re-entry (CCE) as a candidate mechanism underlying the increased vulnerability of Rb-deficient neurons to cell death. Notably, mouse models may limit the extent to which CCE due to Rb inactivation can mimic the pathological course of these disorders, such as Alzheimer's disease. These remarks ought to be considered in future research when studying the consequences of Rb inactivation on neuronal generation and survival in rodents and their corresponding clinical significance in humans.
Language	English
Publishing date	2023-01-13
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	2665-945X
ISSN (online)	2665-945X
DOI	10.1016/j.crneur.2023.100074
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: Stabilization of 14-3-3 protein-protein interactions with Fusicoccin-A decreases alpha-synuclein dependent cell-autonomous death in neuronal and mouse models.

Vinueza-Gavilanes, Rodrigo / Bravo-González, Jorge Juan / Basurco, Leyre / Boncristiani, Chiara / Fernández-Irigoyen, Joaquín / Santamaría, Enrique / Marcilla, Irene / Pérez-Mediavilla, Alberto / Luquin, María Rosario / Vales, Africa / González-Aseguinolaza, Gloria / Aymerich, María Soledad / Aragón, Tomás / Arrasate, Montserrat

Neurobiology of disease

2023 Volume 183, Page(s) 106166

Abstract: ... cause familial cases of synucleinopathies. However, the specific molecular mechanisms of aSyn-dependent ... with aSyn protein levels in brain regions of a transgenic mouse model overexpressing WT human aSyn. Using ... protein interactions (PPIs) that could either promote neuronal death or belong to a coping response ...

Abstract	Synucleinopathies are a group of neurodegenerative diseases without effective treatment characterized by the abnormal aggregation of alpha-synuclein (aSyn) protein. Changes in levels or in the amino acid sequence of aSyn (by duplication/triplication of the aSyn gene or point mutations in the encoding region) cause familial cases of synucleinopathies. However, the specific molecular mechanisms of aSyn-dependent toxicity remain unclear. Increased aSyn protein levels or pathological mutations may favor abnormal protein-protein interactions (PPIs) that could either promote neuronal death or belong to a coping response program against neurotoxicity. Therefore, the identification and modulation of aSyn-dependent PPIs can provide new therapeutic targets for these diseases. To identify aSyn-dependent PPIs we performed a proximity biotinylation assay based on the promiscuous biotinylase BioID2. When expressed as a fusion protein, BioID2 biotinylates by proximity stable and transient interacting partners, allowing their identification by streptavidin affinity purification and mass spectrometry. The aSyn interactome was analyzed using BioID2-tagged wild-type (WT) and pathological mutant E46K aSyn versions in HEK293 cells. We found the 14-3-3 epsilon isoform as a common protein interactor for WT and E46K aSyn. 14-3-3 epsilon correlates with aSyn protein levels in brain regions of a transgenic mouse model overexpressing WT human aSyn. Using a neuronal model in which aSyn cell-autonomous toxicity is quantitatively scored by longitudinal survival analysis, we found that stabilization of 14-3-3 protein-proteins interactions with Fusicoccin-A (FC-A) decreases aSyn-dependent toxicity. Furthermore, FC-A treatment protects dopaminergic neuronal somas in the substantia nigra of a Parkinson's disease mouse model. Based on these results, we propose that the stabilization of 14-3-3 epsilon interaction with aSyn might reduce aSyn toxicity, and highlight FC-A as a potential therapeutic compound for synucleinopathies.
MeSH term(s)	Mice ; Humans ; Animals ; alpha-Synuclein/metabolism ; Synucleinopathies ; 14-3-3 Proteins/genetics ; 14-3-3 Proteins/metabolism ; HEK293 Cells ; Mice, Transgenic ; Dopaminergic Neurons/metabolism
Chemical Substances	alpha-Synuclein ; 14-3-3 Proteins ; fusicoccin (20108-30-9)
Language	English
Publishing date	2023-05-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1211786-9
ISSN	1095-953X ; 0969-9961
ISSN (online)	1095-953X
ISSN	0969-9961
DOI	10.1016/j.nbd.2023.106166
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

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Protective Effects of Cannabinoid Type 2 Receptor Activation Against Microglia Overactivation and Neuronal Pyroptosis in Sepsis-Associated Encephalopathy.

Yang, Liu / Li, Zhen / Xu, Zujin / Zhang, Bin / Liu, Anpeng / He, Qianwen / Zheng, Feng / Zhan, Jia

Neuroscience

2022 Volume 493, Page(s) 99–108

Abstract: ... in neuronal protection and survival promotion. Microglia play a role in CB2R mediated neuronal protection ... pyroptosis, aggravating brain tissue destruction and cognitive dysfunction. The CB2R-specific agonist HU308 ... when neurons are exposed to noxious stimuli. Pyroptosis is a type of programmed proinflammatory cell death ...

Abstract	Sepsis-associated encephalopathy (SAE) has close association with long-term cognitive deficits, resulting in increased mortality. The mechanism of SAE is complicated, including excessive microglial activation and neuroinflammation. Cannabinoid type 2 receptor (CB2R) has been proved to be effective in neuronal protection and survival promotion. Microglia play a role in CB2R mediated neuronal protection when neurons are exposed to noxious stimuli. Pyroptosis is a type of programmed proinflammatory cell death. However, the underlying mechanisms involved in this process still remain to be explored. Here, the SAE model was derived from cecal ligation and puncture (CLP). Tests used to evaluate behavior phenotypes included the open-field test (OFT), novel object recognition test (NORT), and Morris water maze (MWM). Hematoxylin and eosin (H&E) staining, enzyme-linked immunosorbent assays (ELISA), Western blotting, and immunofluorescence staining were performed to detect cell injury, cytokine, CB2R and pyroptosis-associated protein expression. Conclusion from these results, we conclude that CLP could induce microglia hyperactivation and neuronal pyroptosis, aggravating brain tissue destruction and cognitive dysfunction. The CB2R-specific agonist HU308 could have protective effects against SAE by inhibiting microglia activity and neuronal pyroptosis. This study provides a new therapeutic option for the treatment of SAE.
MeSH term(s)	Animals ; Cannabinoids/pharmacology ; Hippocampus/metabolism ; Mice ; Mice, Inbred C57BL ; Microglia/metabolism ; Neurons/metabolism ; Pyroptosis ; Receptor, Cannabinoid, CB2/metabolism ; Sepsis/metabolism ; Sepsis-Associated Encephalopathy/metabolism
Chemical Substances	Cannabinoids ; Receptor, Cannabinoid, CB2
Language	English
Publishing date	2022-04-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	196739-3
ISSN	1873-7544 ; 0306-4522
ISSN (online)	1873-7544
ISSN	0306-4522
DOI	10.1016/j.neuroscience.2022.04.011
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 1215: 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: Neuronal SH2B1 attenuates apoptosis in an MPTP mouse model of Parkinson's disease via promoting PLIN4 degradation

Xiaojuan Han / Yuan Liu / Yan Dai / Tianshu Xu / Qinghui Hu / Xiaolan Yi / Liangyou Rui / Gang Hu / Jun Hu

Redox Biology, Vol 52, Iss , Pp 102308- (2022)

2022

Abstract: ... with Sh2b1 deficiency or neuron-specific Sh2b1 overexpression. Cellular and molecular mechanisms were ... neuronal apoptosis in MPTP-treated mice, whereas restoration of neuron-specific Sh2b1 expression ... survival in an in vivo PD model. Our findings reveal that SH2B1 antagonizes neurodegenerative pathology ...

Abstract	The incidence of Parkinson's disease (PD) has increased tremendously, especially in the aged population and people with metabolic dysfunction; however, its underlying molecular mechanisms remain unclear. SH2B1, an intracellular adaptor protein, contributes to the signal transduction of several receptor tyrosine kinases and exerts beneficial metabolic effects for body weight regulation; however, whether SH2B1 plays a major role in pathological neurodegeneration in PD has not yet been investigated. This study aimed to investigate the effects of SH2B1 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)–induced PD mice with Sh2b1 deficiency or neuron-specific Sh2b1 overexpression. Cellular and molecular mechanisms were elucidated using human dopaminergic neuron SH-SY5Y cells analysed. We found that SH2B1 expression was confirmed to be downregulated in the blood samples of PD patients and in the brains of mice with MPTP-induced chronic PD. Sh2b1 deficiency caused marked exacerbation of behavioural defects and increased neuronal apoptosis in MPTP-treated mice, whereas restoration of neuron-specific Sh2b1 expression significantly reversed these effects. Similar results were observed in MPP + -treated SH-SY5Y cells. Mechanistically, upon binding to heat shock cognate 70 (HSC70), SH2B1 promotes HSC70-related recognition and PLIN4 lysosomal translocation and degradation, thus suppressing lipid peroxidation stress in the brains of PD mice. Adeno-associated virus-mediated rescue of neuronal HSC70 expression functionally alleviated the neuropathology of PD in wild-type but not in Sh2b1-deficient mice. This is the first study to examine the molecular underpinnings of SH2B1 against MPTP-induced neurodegeneration through cell autonomous promotion of neuronal survival in an in vivo PD model. Our findings reveal that SH2B1 antagonizes neurodegenerative pathology in PD via the SH2B1–HSC70–PLIN4 axis.
Keywords	Parkinson's disease ; Heat shock protein ; Neurodegeneration ; SH2B1 ; PLIN4 ; Apoptosis ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

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: Downregulation of Homer1b/c improves neuronal survival after traumatic neuronal injury.

Fei, F / Rao, W / Zhang, L / Chen, B-G / Li, J / Fei, Z / Chen, Z

Neuroscience

2014 Volume 267, Page(s) 187–194

Abstract: ... investigates the role of Homer1b/c in modulating neuronal survival by using an in vitro traumatic neuronal ... significantly (p<0.05) alleviated the cytoplasmic calcium levels and neuron lactate dehydrogenase release, and ... signal transduction pathway, but also regulated the expression of mGluR1a in mechanical neuronal injury. These findings ...

Abstract	Homer protein, a member of the post-synaptic density protein family, plays an important role in the neuronal synaptic activity and is extensively involved in neurological disorders. The present study investigates the role of Homer1b/c in modulating neuronal survival by using an in vitro traumatic neuronal injury model, which was achieved by using a punch device that consisted of 28 stainless steel blades joined together and produced 28 parallel cuts. Downregulation of Homer1b/c by specific siRNA significantly (p<0.05) alleviated the cytoplasmic calcium levels and neuron lactate dehydrogenase release, and ultimately decreased the apoptotic rate after traumatic neuronal injury compared with non-targeting siRNA control treatment in cultured rat cortical neurons. Moreover, the expression of metabotropic glutamate receptor 1a (mGluR1a) was significantly (p<0.05) reduced in the Homer1b/c siRNA-transfected neurons after injury. Therefore, Homer1b/c not only modulated the mGluR1a-inositol 1,4,5-triphosphate receptors-Ca(2+) signal transduction pathway, but also regulated the expression of mGluR1a in mechanical neuronal injury. These findings indicate that the suppression of Homer1b/c expression potentially protects neurons from glutamate excitotoxicity after injury and might be an effective intervention target in traumatic brain injury.
MeSH term(s)	Animals ; Calcium/metabolism ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Cell Survival/physiology ; Cells, Cultured ; Cerebral Cortex/cytology ; Down-Regulation/physiology ; Embryo, Mammalian ; Homer Scaffolding Proteins ; In Situ Nick-End Labeling ; Mixed Function Oxygenases/metabolism ; Neurons/metabolism ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Rats ; Rats, Wistar ; Receptors, Metabotropic Glutamate/metabolism ; Transfection
Chemical Substances	Carrier Proteins ; Homer Scaffolding Proteins ; Homer1 protein, rat ; RNA, Small Interfering ; Receptors, Metabotropic Glutamate ; metabotropic glutamate receptor 3 ; metabotropic glutamate receptor type 1 ; Mixed Function Oxygenases (EC 1.-) ; lactate 2-monooxygenase (EC 1.13.12.4) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2014-05-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	196739-3
ISSN	1873-7544 ; 0306-4522
ISSN (online)	1873-7544
ISSN	0306-4522
DOI	10.1016/j.neuroscience.2014.02.037
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 1215: 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: Astrocyte inflammatory signaling mediates α-synuclein aggregation and dopaminergic neuronal loss following viral encephalitis.

Bantle, Collin M / Rocha, Savannah M / French, C Tenley / Phillips, Aaron T / Tran, Kevin / Olson, Kenneth E / Bass, Todd A / Aboellail, Tawfik / Smeyne, Richard J / Tjalkens, Ronald B

Experimental neurology

2021 Volume 346, Page(s) 113845

Abstract: ... neuronal loss and protein aggregation across multiple brain regions, including the substantia nigra pars ... in surviving patients and can present with symptoms resembling Parkinson's disease (PD). The mechanisms ... activation of microglia and astrocytes that precipitates widespread aggregation of α-synuclein in the brain ...

Abstract	Viral infection of the central nervous system (CNS) can cause lasting neurological decline in surviving patients and can present with symptoms resembling Parkinson's disease (PD). The mechanisms underlying postencephalitic parkinsonism remain unclear but are thought to involve increased innate inflammatory signaling in glial cells, resulting in persistent neuroinflammation. We therefore studied the role of glial cells in regulating neuropathology in postencephalitic parkinsonism by studying the involvement of astrocytes in loss of dopaminergic neurons and aggregation of α-synuclein protein following infection with western equine encephalitis virus (WEEV). Infections were conducted in both wildtype mice and in transgenic mice lacking NFκB inflammatory signaling in astrocytes. For 2 months following WEEV infection, we analyzed glial activation, neuronal loss and protein aggregation across multiple brain regions, including the substantia nigra pars compacta (SNpc). These data revealed that WEEV induces loss of SNpc dopaminergic neurons, persistent activation of microglia and astrocytes that precipitates widespread aggregation of α-synuclein in the brain of C57BL/6 mice. Microgliosis and macrophage infiltration occurred prior to activation of astrocytes and was followed by opsonization of ⍺-synuclein protein aggregates in the cortex, hippocampus and midbrain by the complement protein, C3. Astrocyte-specific NFκB knockout mice had reduced gliosis, α-synuclein aggregate formation and neuronal loss. These data suggest that astrocytes play a critical role in initiating PD-like pathology following encephalitic infection with WEEV through innate immune inflammatory pathways that damage dopaminergic neurons, possibly by hindering clearance of ⍺-synuclein aggregates. Inhibiting glial inflammatory responses could therefore represent a potential therapy strategy for viral parkinsonism.
MeSH term(s)	Animals ; Astrocytes/immunology ; Astrocytes/metabolism ; Dopaminergic Neurons/immunology ; Dopaminergic Neurons/metabolism ; Encephalitis Virus, Western Equine/immunology ; Encephalitis Virus, Western Equine/metabolism ; Encephalitis, Viral/immunology ; Encephalitis, Viral/metabolism ; Female ; Humans ; Inflammation Mediators/immunology ; Inflammation Mediators/metabolism ; Male ; Mice ; Mice, Knockout ; Protein Aggregates/physiology ; Signal Transduction/physiology ; alpha-Synuclein/metabolism
Chemical Substances	Inflammation Mediators ; Protein Aggregates ; alpha-Synuclein
Language	English
Publishing date	2021-08-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	207148-4
ISSN	1090-2430 ; 0014-4886
ISSN (online)	1090-2430
ISSN	0014-4886
DOI	10.1016/j.expneurol.2021.113845
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 184: 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: Caregiver maltreatment causes altered neuronal DNA methylation in female rodents.

Blaze, Jennifer / Roth, Tania L

Development and psychopathology

2017 Volume 29, Issue 2, Page(s) 477–489

Abstract: ... induced methylation of DNA associated with Bdnf IV in a cell-type and sex-specific manner. Specifically ... Negative experiences with a caregiver during infancy can result in long-term changes in brain ... that brain and behavior changes are conferred by early childhood adversity through epigenetic changes ...

Abstract	Negative experiences with a caregiver during infancy can result in long-term changes in brain function and behavior, but underlying mechanisms are not well understood. It is our central hypothesis that brain and behavior changes are conferred by early childhood adversity through epigenetic changes involving DNA methylation. Using a rodent model of early-life caregiver maltreatment (involving exposure to an adverse caregiving environment for postnatal days 1-7), we have previously demonstrated abnormal methylation of DNA associated with the brain-derived neurotrophic factor (Bdnf) gene in the medial prefrontal cortex (mPFC) of adult rats. The aim of the current study was to characterize Bdnf DNA methylation in specific cell populations within the mPFC. In the prefrontal cortex, there is approximately twice as many neurons as glia, and studies have recently shown differential and distinctive DNA methylation patterns in neurons versus nonneurons. Here, we extracted nuclei from the mPFC of adult animals that had experienced maltreatment and used fluorescence-activated cell sorting to isolate cell types before performing bisulfite sequencing to estimate methylation of cytosine-guanine sites. Our data indicate that early-life stress induced methylation of DNA associated with Bdnf IV in a cell-type and sex-specific manner. Specifically, females that experienced early-life maltreatment exhibited greater neuronal cytosine-guanine methylation compared to controls, while no changes were detected in Bdnf methylation in males regardless of cell type. These changes localize the specificity of our previous findings to mPFC neurons and highlight the capacity of maltreatment to cause methylation changes that are likely to have functional consequences for neuronal function.
MeSH term(s)	Adult Survivors of Child Abuse ; Animals ; Brain-Derived Neurotrophic Factor/metabolism ; DNA Methylation ; Disease Models, Animal ; Female ; Humans ; Male ; Neurons/metabolism ; Prefrontal Cortex/cytology ; Prefrontal Cortex/metabolism ; Rats ; Rats, Long-Evans ; Sex Factors ; Stress, Psychological/metabolism
Chemical Substances	Brain-Derived Neurotrophic Factor ; BDNF protein, human (7171WSG8A2)
Language	English
Publishing date	2017-05-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	1036173-x
ISSN	1469-2198 ; 0954-5794
ISSN (online)	1469-2198
ISSN	0954-5794
DOI	10.1017/S0954579417000128
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 2601: 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

Details ▾

To top

More links

Kategorien

Order via subito

Full text online

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

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

Full text online

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

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito