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  1. AU="Bosch, Peter J"
  2. AU="Colin R. Jackson" AU="Colin R. Jackson"
  3. AU="Tan, Bruce K"
  4. AU="Alagappan, Annamalai"
  5. AU="Howard, Lauren L."
  6. AU=Nataraj Gita AU=Nataraj Gita
  7. AU="Zi-Lan Wang"
  8. AU="John F. Whitesides"
  9. AU="Kim, Eun-Kyu"
  10. AU="Shapiro, Anne Nicole"
  11. AU="Joseph R. Francica"
  12. AU="Stringer, Kathleen A."
  13. AU="López-Cobo, Sheila"
  14. AU="Sznitman, Raphael"
  15. AU="Philippe Ciais"
  16. AU="Suprasert, Prapaporn"
  17. AU="Chang, Yinshui"
  18. AU="de Oliveira, Alexandre Adalardo"
  19. AU="D'Angelo Exeni, Maria Eugenia"
  20. AU="Godoy, Carla"

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  1. Artikel ; Online: Enhanced Spine Stability and Survival Lead to Increases in Dendritic Spine Density as an Early Response to Local Alpha-Synuclein Overexpression in Mouse Prefrontal Cortex.

    Bosch, Peter J / Kerr, Gemma / Cole, Rachel / Warwick, Charles A / Wendt, Linder H / Pradeep, Akash / Bagnall, Emma / Aldridge, Georgina M

    Cellular and molecular neurobiology

    2024  Band 44, Heft 1, Seite(n) 42

    Abstract: Lewy Body Dementias (LBD), including Parkinson's disease dementia and Dementia with Lewy Bodies, are characterized by widespread accumulation of intracellular alpha-Synuclein protein deposits in regions beyond the brainstem, including in the cortex. ... ...

    Abstract Lewy Body Dementias (LBD), including Parkinson's disease dementia and Dementia with Lewy Bodies, are characterized by widespread accumulation of intracellular alpha-Synuclein protein deposits in regions beyond the brainstem, including in the cortex. However, the impact of local pathology in the cortex is unknown. To investigate this, we employed viral overexpression of human alpha-Synuclein protein targeting the mouse prefrontal cortex (PFC). We then used in vivo 2-photon microscopy to image awake head-fixed mice via an implanted chronic cranial window to assess the early consequences of alpha-Synuclein overexpression in the weeks following overexpression. We imaged apical tufts of Layer V pyramidal neurons in the PFC of Thy1-YFP transgenic mice at 1-week intervals from 1 to 2 weeks before and 9 weeks following viral overexpression, allowing analysis of dynamic changes in dendritic spines. We found an increase in the relative dendritic spine density following local overexpression of alpha-Synuclein, beginning at 5 weeks post-injection, and persisting for the remainder of the study. We found that alpha-Synuclein overexpression led to an increased percentage and longevity of newly-persistent spines, without significant changes in the total density of newly formed or eliminated spines. A follow-up study utilizing confocal microscopy revealed that the increased spine density is found in cortical cells within the alpha-Synuclein injection site, but negative for alpha-Synuclein phosphorylation at Serine-129, highlighting the potential for effects of dose and local circuits on spine survival. These findings have important implications for the physiological role and early pathological stages of alpha-Synuclein in the cortex.
    Mesh-Begriff(e) Animals ; Humans ; Male ; Mice ; alpha-Synuclein/metabolism ; Cell Survival/physiology ; Dendritic Spines/metabolism ; Mice, Inbred C57BL ; Mice, Transgenic ; Prefrontal Cortex/metabolism ; Prefrontal Cortex/pathology ; Pyramidal Cells/metabolism ; Pyramidal Cells/pathology
    Chemische Substanzen alpha-Synuclein ; Snca protein, mouse
    Sprache Englisch
    Erscheinungsdatum 2024-04-26
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 283404-2
    ISSN 1573-6830 ; 0272-4340
    ISSN (online) 1573-6830
    ISSN 0272-4340
    DOI 10.1007/s10571-024-01472-7
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: Enhanced spine stability and survival lead to increases in dendritic spine density as an early response to local alpha-synuclein overexpression in mouse prefrontal cortex.

    Bosch, Peter J / Kerr, Gemma / Cole, Rachel / Warwick, Charles A / Wendt, Linder H / Pradeep, Akash / Bagnall, Emma / Aldridge, Georgina M

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Lewy Body Dementias (LBD), including Parkinson's disease dementia and Dementia with Lewy Bodies, are characterized by widespread accumulation of intracellular alpha-Synuclein protein deposits in regions beyond the brainstem, including in the cortex. ... ...

    Abstract Lewy Body Dementias (LBD), including Parkinson's disease dementia and Dementia with Lewy Bodies, are characterized by widespread accumulation of intracellular alpha-Synuclein protein deposits in regions beyond the brainstem, including in the cortex. Patients with LBDs develop cognitive changes, including abnormalities in executive function, attention, hallucinations, slowed processing, and cognitive fluctuations. The causes of these non-motor symptoms remain unclear; however, accumulation of alpha-Synuclein aggregates in the cortex and subsequent interference of synaptic and cellular function could contribute to psychiatric and cognitive symptoms. It is unknown how the cortex responds to local pathology in the absence of significant secondary effects of alpha-Synuclein pathology in the brainstem. To investigate this, we employed viral overexpression of human alpha-Synuclein protein targeting the mouse prefrontal cortex (PFC). We then used
    Sprache Englisch
    Erscheinungsdatum 2023-09-28
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2023.09.28.559765
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: A critical role for the nuclear protein Akirin2 in the formation of mammalian muscle in vivo.

    Bosch, Peter J / Fuller, Leah C / Weiner, Joshua A

    Genesis (New York, N.Y. : 2000)

    2019  Band 57, Heft 5, Seite(n) e23286

    Abstract: Evolutionarily conserved Akirin nuclear proteins interact with chromatin remodeling complexes at gene enhancers and promoters, and have been reported to regulate cell proliferation and differentiation. Of the two mouse Akirin genes, Akirin2 is essential ... ...

    Abstract Evolutionarily conserved Akirin nuclear proteins interact with chromatin remodeling complexes at gene enhancers and promoters, and have been reported to regulate cell proliferation and differentiation. Of the two mouse Akirin genes, Akirin2 is essential during embryonic development, with known in vivo roles in immune system function and the formation of the cerebral cortex. Here we demonstrate that Akirin2 is critical for mouse myogenesis, a tightly regulated developmental process through which myoblast precursors fuse to form mature skeletal muscle fibers. Loss of Akirin2 in somitic muscle precursor cells via Sim1-Cre-mediated excision of a conditional Akirin2 allele results in neonatal lethality. Mutant embryos exhibit a complete lack of forelimb, intercostal, and diaphragm muscles due to extensive apoptosis and loss of Pax3-positive myoblasts. Severe skeletal defects, including craniofacial abnormalities, disrupted ossification, and rib fusions are also observed, attributable to lack of skeletal muscles as well as patchy Sim1-Cre activity in the embryonic sclerotome. We further show that Akirin2 levels are tightly regulated during muscle cell differentiation in vitro, and that Akirin2 is required for the proper expression of muscle differentiation factors myogenin and myosin heavy chain. Our results implicate Akirin2 as a major regulator of mammalian muscle formation in vivo.
    Mesh-Begriff(e) Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Cell Differentiation ; Cell Proliferation ; Embryo, Mammalian ; Embryonic Development ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle Cells/metabolism ; Muscle Cells/physiology ; Muscle Development/physiology ; Muscle, Skeletal/metabolism ; Muscles/metabolism ; Myoblasts/metabolism ; Myosin Heavy Chains/genetics ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Promoter Regions, Genetic/genetics ; Repressor Proteins/genetics ; Repressor Proteins/metabolism ; Repressor Proteins/physiology ; Signal Transduction ; Transcription Factors/genetics
    Chemische Substanzen Akirin2 protein, mouse ; Basic Helix-Loop-Helix Transcription Factors ; Nuclear Proteins ; Repressor Proteins ; Transcription Factors ; Myosin Heavy Chains (EC 3.6.4.1)
    Sprache Englisch
    Erscheinungsdatum 2019-03-12
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2004544-X
    ISSN 1526-968X ; 1526-954X
    ISSN (online) 1526-968X
    ISSN 1526-954X
    DOI 10.1002/dvg.23286
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Akirin proteins in development and disease: critical roles and mechanisms of action.

    Bosch, Peter J / Peek, Stacey L / Smolikove, Sarit / Weiner, Joshua A

    Cellular and molecular life sciences : CMLS

    2020  Band 77, Heft 21, Seite(n) 4237–4254

    Abstract: The Akirin genes, which encode small, nuclear proteins, were first characterized in 2008 in Drosophila and rodents. Early studies demonstrated important roles in immune responses and tumorigenesis, which subsequent work found to be highly conserved. More ...

    Abstract The Akirin genes, which encode small, nuclear proteins, were first characterized in 2008 in Drosophila and rodents. Early studies demonstrated important roles in immune responses and tumorigenesis, which subsequent work found to be highly conserved. More recently, a multiplicity of Akirin functions, and the associated molecular mechanisms involved, have been uncovered. Here, we comprehensively review what is known about invertebrate Akirin and its two vertebrate homologues Akirin1 and Akirin2, highlighting their role in regulating gene expression changes across a number of biological systems. We detail essential roles for Akirin family proteins in the development of the brain, limb, and muscle, in meiosis, and in tumorigenesis, emphasizing associated signaling pathways. We describe data supporting the hypothesis that Akirins act as a "bridge" between a variety of transcription factors and major chromatin remodeling complexes, and discuss several important questions remaining to be addressed. In little more than a decade, Akirin proteins have gone from being completely unknown to being increasingly recognized as evolutionarily conserved mediators of gene expression programs essential for the formation and function of animals.
    Mesh-Begriff(e) Adaptor Proteins, Signal Transducing/analysis ; Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Brain/metabolism ; Cell Cycle ; Cell Proliferation ; DNA-Binding Proteins/analysis ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Gene Expression Regulation ; Humans ; Muscle Development ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Nuclear Proteins/analysis ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Signal Transduction ; Transcription Factors/analysis ; Transcription Factors/genetics ; Transcription Factors/metabolism
    Chemische Substanzen AKIRIN1 protein, human ; Adaptor Proteins, Signal Transducing ; DNA-Binding Proteins ; Nuclear Proteins ; Transcription Factors ; ZBTB7A protein, human
    Sprache Englisch
    Erscheinungsdatum 2020-05-02
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Review
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-020-03531-w
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Stay or go? Neuronal activity in medial frontal cortex during a voluntary tactile preference task in head-fixed mice.

    Keyes, Alex L / Kim, Young-Cho / Bosch, Peter J / Usachev, Yuriy M / Aldridge, Georgina M

    Cell calcium

    2021  Band 96, Seite(n) 102388

    Abstract: The decision to move is influenced by sensory, attentional, and motivational cues. One such cue is the quality of the tactile input, with noxious or unpleasant sensations causing an animal to move away from the cue. Processing of painful and unpleasant ... ...

    Abstract The decision to move is influenced by sensory, attentional, and motivational cues. One such cue is the quality of the tactile input, with noxious or unpleasant sensations causing an animal to move away from the cue. Processing of painful and unpleasant sensation in the cortex involves multiple brain regions, although the specific role of the brain areas involved in voluntary, rather than reflexive movement away from unpleasant stimuli is not well understood. Here, we focused on the medial subdivision of secondary motor cortex, which is proposed to link sensory and contextual cues to motor action, and tested its role in controlling voluntary movement in the context of an aversive tactile cue. We designed a novel, 3D-printed tactile platform consisting of innocuous (grid) and mildly noxious (spiked) surfaces (50:50 % of total area), which enabled monitoring neuronal activity in the medial frontal cortex by two-photon imaging during a sensory preference task in head-fixed mice. We found that freely moving mice spent significantly less time on a spiked-surface, and that this preference was eliminated by administration of a local anesthetic. At the neuronal level, individual neurons were differentially modulated specific to the tactile surface encountered. At the population level, the neuronal activity was analyzed in relation to the events where mice chose to "stop-on" or "go-from" a specific tactile surface and when they "switched" surfaces without stopping. Notably, each of these three scenarios showed population activity that differed significantly between the grid and spiked tactile surfaces. Collectively, these data provide evidence that tactile quality is encoded within medial frontal cortex. The task pioneered in this study provides a valuable tool to better evaluate mouse models of nociception and pain, using a voluntary task that allows simultaneous recording of preference and choice.
    Mesh-Begriff(e) Animals ; Choice Behavior/physiology ; Female ; Frontal Lobe/chemistry ; Frontal Lobe/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Microscopy, Fluorescence, Multiphoton/methods ; Neurons/chemistry ; Neurons/physiology ; Psychomotor Performance/physiology ; Stereotaxic Techniques ; Touch/physiology
    Sprache Englisch
    Erscheinungsdatum 2021-03-04
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 757687-0
    ISSN 1532-1991 ; 0143-4160
    ISSN (online) 1532-1991
    ISSN 0143-4160
    DOI 10.1016/j.ceca.2021.102388
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel: Akirin proteins in development and disease: critical roles and mechanisms of action

    Bosch, Peter J / Peek, Stacey L / Smolikove, Sarit / Weiner, Joshua A

    Cellular and molecular life sciences. 2020 Nov., v. 77, no. 21

    2020  

    Abstract: The Akirin genes, which encode small, nuclear proteins, were first characterized in 2008 in Drosophila and rodents. Early studies demonstrated important roles in immune responses and tumorigenesis, which subsequent work found to be highly conserved. More ...

    Abstract The Akirin genes, which encode small, nuclear proteins, were first characterized in 2008 in Drosophila and rodents. Early studies demonstrated important roles in immune responses and tumorigenesis, which subsequent work found to be highly conserved. More recently, a multiplicity of Akirin functions, and the associated molecular mechanisms involved, have been uncovered. Here, we comprehensively review what is known about invertebrate Akirin and its two vertebrate homologues Akirin1 and Akirin2, highlighting their role in regulating gene expression changes across a number of biological systems. We detail essential roles for Akirin family proteins in the development of the brain, limb, and muscle, in meiosis, and in tumorigenesis, emphasizing associated signaling pathways. We describe data supporting the hypothesis that Akirins act as a “bridge” between a variety of transcription factors and major chromatin remodeling complexes, and discuss several important questions remaining to be addressed. In little more than a decade, Akirin proteins have gone from being completely unknown to being increasingly recognized as evolutionarily conserved mediators of gene expression programs essential for the formation and function of animals.
    Schlagwörter Drosophila ; brain ; carcinogenesis ; chromatin ; gene expression ; invertebrates ; meiosis ; muscles
    Sprache Englisch
    Erscheinungsverlauf 2020-11
    Umfang p. 4237-4254.
    Erscheinungsort Springer International Publishing
    Dokumenttyp Artikel
    Anmerkung NAL-AP-2-clean ; Review
    ZDB-ID 1358415-7
    ISSN 1420-9071 ; 1420-682X
    ISSN (online) 1420-9071
    ISSN 1420-682X
    DOI 10.1007/s00018-020-03531-w
    Datenquelle NAL Katalog (AGRICOLA)

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  7. Artikel ; Online: An essential role for the nuclear protein Akirin2 in mouse limb interdigital tissue regression.

    Bosch, Peter J / Fuller, Leah C / Weiner, Joshua A

    Scientific reports

    2018  Band 8, Heft 1, Seite(n) 12240

    Abstract: The regulation of interdigital tissue regression requires the interplay of multiple spatiotemporally-controlled morphogen gradients to ensure proper limb formation and release of individual digits. Disruption to this process can lead to a number of limb ... ...

    Abstract The regulation of interdigital tissue regression requires the interplay of multiple spatiotemporally-controlled morphogen gradients to ensure proper limb formation and release of individual digits. Disruption to this process can lead to a number of limb abnormalities, including syndactyly. Akirins are highly conserved nuclear proteins that are known to interact with chromatin remodelling machinery at gene enhancers. In mammals, the analogue Akirin2 is essential for embryonic development and critical for a wide variety of roles in immune function, meiosis, myogenesis and brain development. Here we report a critical role for Akirin2 in the regulation of interdigital tissue regression in the mouse limb. Knockout of Akirin2 in limb epithelium leads to a loss of interdigital cell death and an increase in cell proliferation, resulting in retention of the interdigital web and soft-tissue syndactyly. This is associated with perdurance of Fgf8 expression in the ectoderm overlying the interdigital space. Our study supports a mechanism whereby Akirin2 is required for the downregulation of Fgf8 from the apical ectodermal ridge (AER) during limb development, and implies its requirement in signalling between interdigital mesenchymal cells and the AER.
    Mesh-Begriff(e) Animals ; Cell Proliferation ; Extremities/growth & development ; Fibroblast Growth Factor 8/metabolism ; Gene Expression Regulation, Developmental ; Gene Knockout Techniques ; Mice ; Repressor Proteins/deficiency ; Repressor Proteins/genetics ; Repressor Proteins/metabolism ; Signal Transduction
    Chemische Substanzen Akirin2 protein, mouse ; Fgf8 protein, mouse ; Repressor Proteins ; Fibroblast Growth Factor 8 (148997-75-5)
    Sprache Englisch
    Erscheinungsdatum 2018-08-16
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-018-30801-2
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; Online: A Unique Role for Protocadherin γC3 in Promoting Dendrite Arborization through an Axin1-Dependent Mechanism.

    Steffen, David M / Hanes, Camille M / Mah, Kar Men / Valiño Ramos, Paula / Bosch, Peter J / Hinz, Dalton C / Radley, Jason J / Burgess, Robert W / Garrett, Andrew M / Weiner, Joshua A

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

    2023  Band 43, Heft 6, Seite(n) 918–935

    Abstract: The establishment of a functional cerebral cortex depends on the proper execution of multiple developmental steps, culminating in dendritic and axonal outgrowth and the formation and maturation of synaptic connections. Dysregulation of these processes ... ...

    Abstract The establishment of a functional cerebral cortex depends on the proper execution of multiple developmental steps, culminating in dendritic and axonal outgrowth and the formation and maturation of synaptic connections. Dysregulation of these processes can result in improper neuronal connectivity, including that associated with various neurodevelopmental disorders. The γ-Protocadherins (γ-Pcdhs), a family of 22 distinct cell adhesion molecules that share a C-terminal cytoplasmic domain, are involved in multiple aspects of neurodevelopment including neuronal survival, dendrite arborization, and synapse development. The extent to which individual γ-Pcdh family members play unique versus common roles remains unclear. We demonstrated previously that the γ-Pcdh-C3 isoform (γC3), via its unique "variable" cytoplasmic domain (VCD), interacts in cultured cells with Axin1, a Wnt-pathway scaffold protein that regulates the differentiation and morphology of neurons. Here, we confirm that γC3 and Axin1 interact in the cortex
    Mesh-Begriff(e) Animals ; Female ; Male ; Mice ; Axin Protein/metabolism ; Cadherins/metabolism ; Cell Adhesion Molecules/metabolism ; Dendrites/physiology ; Mice, Knockout ; Neuronal Plasticity ; Protein Isoforms/genetics ; Protein Isoforms/metabolism ; Protocadherins
    Chemische Substanzen Axin Protein ; Axin1 protein, mouse ; Cadherins ; Cell Adhesion Molecules ; Protein Isoforms ; Protocadherins ; Pcdhgc3 protein, mouse
    Sprache Englisch
    Erscheinungsdatum 2023-01-05
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 604637-x
    ISSN 1529-2401 ; 0270-6474
    ISSN (online) 1529-2401
    ISSN 0270-6474
    DOI 10.1523/JNEUROSCI.0729-22.2022
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; Online: Proteomics Analysis of Dorsal Striatum Reveals Changes in Synaptosomal Proteins following Methamphetamine Self-Administration in Rats.

    Bosch, Peter J / Peng, Lifeng / Kivell, Bronwyn M

    PloS one

    2015  Band 10, Heft 10, Seite(n) e0139829

    Abstract: Methamphetamine is a widely abused, highly addictive drug. Regulation of synaptic proteins within the brain's reward pathway modulates addiction behaviours, the progression of drug addiction and long-term changes in brain structure and function that ... ...

    Abstract Methamphetamine is a widely abused, highly addictive drug. Regulation of synaptic proteins within the brain's reward pathway modulates addiction behaviours, the progression of drug addiction and long-term changes in brain structure and function that result from drug use. Therefore, using large scale proteomics studies we aim to identify global protein expression changes within the dorsal striatum, a key brain region involved in the modulation of addiction. We performed LC-MS/MS analyses on rat striatal synaptosomes following 30 days of methamphetamine self-administration (2 hours/day) and 14 days abstinence. We identified a total of 84 differentially-expressed proteins with known roles in neuroprotection, neuroplasticity, cell cytoskeleton, energy regulation and synaptic vesicles. We identify significant expression changes in stress-induced phosphoprotein and tubulin polymerisation-promoting protein, which have not previously been associated with addiction. In addition, we confirm the role of amphiphysin and phosphatidylethanolamine binding protein in addiction. This approach has provided new insight into the effects of methamphetamine self-administration on synaptic protein expression in a key brain region associated with addiction, showing a large set of differentially-expressed proteins that persist into abstinence. The mass spectrometry proteomics data are available via ProteomeXchange with identifier PXD001443.
    Mesh-Begriff(e) Animals ; Central Nervous System Stimulants/administration & dosage ; Corpus Striatum/drug effects ; Corpus Striatum/metabolism ; Male ; Methamphetamine/administration & dosage ; Proteomics ; Rats ; Rats, Sprague-Dawley ; Self Administration ; Synaptosomes/drug effects ; Synaptosomes/metabolism ; Tandem Mass Spectrometry
    Chemische Substanzen Central Nervous System Stimulants ; Methamphetamine (44RAL3456C)
    Sprache Englisch
    Erscheinungsdatum 2015
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0139829
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel ; Online: p53-mediated neurodegeneration in the absence of the nuclear protein Akirin2.

    Peek, Stacey L / Bosch, Peter J / Bahl, Ethan / Iverson, Brianna J / Parida, Mrutyunjaya / Bais, Preeti / Manak, J Robert / Michaelson, Jacob J / Burgess, Robert W / Weiner, Joshua A

    iScience

    2022  Band 25, Heft 2, Seite(n) 103814

    Abstract: Proper gene regulation is critical for both neuronal development and maintenance as the brain matures. We previously demonstrated that Akirin2, an essential nuclear protein that interacts with transcription factors and chromatin remodeling complexes, is ... ...

    Abstract Proper gene regulation is critical for both neuronal development and maintenance as the brain matures. We previously demonstrated that Akirin2, an essential nuclear protein that interacts with transcription factors and chromatin remodeling complexes, is required for the embryonic formation of the cerebral cortex. Here we show that Akirin2 plays a mechanistically distinct role in maintaining healthy neurons during cortical maturation. Restricting Akirin2 loss to excitatory cortical neurons resulted in progressive neurodegeneration via necroptosis and severe cortical atrophy with age. Comparing transcriptomes from Akirin2-null postnatal neurons and cortical progenitors revealed that targets of the tumor suppressor p53, a regulator of both proliferation and cell death encoded by
    Sprache Englisch
    Erscheinungsdatum 2022-01-25
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2022.103814
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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