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  1. Article ; Online: A novel approach to generate enzyme-free single cell suspensions from archived tissues for miRNA sequencing.

    Scheuermann, Stefan / Hücker, Sarah / Engel, Annika / Ludwig, Nicole / Lebhardt, Philipp / Langejürgen, Jens / Kirsch, Stefan

    SLAS technology

    2024  , Page(s) 100133

    Abstract: Obtaining high-quality omics data at the single-cell level from archived human tissue samples is crucial for gaining insights into cellular heterogeneity and pushing the field of personalized medicine forward. In this technical brief we present a ... ...

    Abstract Obtaining high-quality omics data at the single-cell level from archived human tissue samples is crucial for gaining insights into cellular heterogeneity and pushing the field of personalized medicine forward. In this technical brief we present a comprehensive methodological framework for the efficient enzyme-free preparation of tissue-derived single cell suspensions and their conversion into single-cell miRNA sequencing libraries. The resulting data from this study have the potential to deepen our understanding of miRNA expression at the single-cell level and its relevance in the context of the examined tissues. The workflow encompasses tissue collection, RNALater immersion, storage, thawing, TissueGrinder-mediated dissociation, miRNA lysis, library preparation, sequencing, and data analysis. Quality control measures ensure reliable miRNA data, with specific attention to sample quality. The UMAP analysis reveals tissue-specific cell clustering, while miRNA diversity reflects tissue variations. The presented workflow effectively processes preserved tissues, extending opportunities for retrospective analysis and biobank utilization.
    Language English
    Publishing date 2024-04-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2900310-6
    ISSN 2472-6311 ; 2472-6303
    ISSN (online) 2472-6311
    ISSN 2472-6303
    DOI 10.1016/j.slast.2024.100133
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Book ; Online ; Thesis: Combining Optogenetics and fMRI to Study Cerebral Networks in Animal Models

    Lebhardt, Philipp [Verfasser] / Sartorius, Alexander [Akademischer Betreuer]

    2017  

    Author's details Philipp Lebhardt ; Betreuer: Alexander Sartorius
    Keywords Psychologie ; Psychology
    Subject code sg150
    Language English
    Publisher Universitätsbibliothek Heidelberg
    Publishing place Heidelberg
    Document type Book ; Online ; Thesis
    Database Digital theses on the web

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  3. Article ; Online: Optogenetic fMRI in the mouse hippocampus: Hemodynamic response to brief glutamatergic stimuli.

    Lebhardt, Philipp / Hohenberg, Christian Clemm von / Weber-Fahr, Wolfgang / Kelsch, Wolfgang / Sartorius, Alexander

    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

    2016  Volume 36, Issue 3, Page(s) 629–638

    Abstract: The combination of optogenetics with functional magnetic resonance imaging is a promising tool to study the causal relationship between specific neuronal populations and global brain activity. We employed this technique to study the brain response to ... ...

    Abstract The combination of optogenetics with functional magnetic resonance imaging is a promising tool to study the causal relationship between specific neuronal populations and global brain activity. We employed this technique to study the brain response to recruitment of glutamatergic neurons in the mouse hippocampus. The light-sensitive protein channelrhodopsin-2 was expressed in α-CamKII-positive glutamatergic neurons in the left hippocampus (N = 10). Functional magnetic resonance imaging was performed during local laser stimulation, with stimulus duration of 1 second. The hemodynamic response to these stimuli was analyzed on a whole-brain level. In a secondary analysis, we examined the impact of the stimulation locus on the dorso-ventral axis within the hippocampal formation. The hemodynamic response in the mouse hippocampus had an earlier peak and a shorter duration compared to those observed in humans. Photostimulation was associated with significantly increased blood oxygen level-dependent signal in group statistics: bilaterally in the hippocampus, frontal lobe and septum, ipsilaterally in the nucleus accumbens and contralaterally in the striatum. More dorsal position of the laser fiber was associated with a stronger activation in projection regions (insular cortex and striatum). The characterization of brain-region-specific hemodynamic response functions may enable more precise interpretation of future functional magnetic resonance imaging experiments.
    MeSH term(s) Animals ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics ; Channelrhodopsins ; Gene Expression ; Glutamic Acid/metabolism ; Hemodynamics ; Hippocampus/blood supply ; Hippocampus/cytology ; Hippocampus/physiology ; Magnetic Resonance Imaging/methods ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neurons/cytology ; Neurons/metabolism ; Optogenetics/methods
    Chemical Substances Channelrhodopsins ; Glutamic Acid (3KX376GY7L) ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 (EC 2.7.11.17) ; Camk2a protein, mouse (EC 2.7.11.17)
    Language English
    Publishing date 2016-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 604628-9
    ISSN 1559-7016 ; 0271-678X
    ISSN (online) 1559-7016
    ISSN 0271-678X
    DOI 10.1177/0271678X15606455
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1663: 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)

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  4. Article ; Online: Lateral habenula perturbation reduces default-mode network connectivity in a rat model of depression.

    Clemm von Hohenberg, Christian / Weber-Fahr, Wolfgang / Lebhardt, Philipp / Ravi, Namasivayam / Braun, Urs / Gass, Natalia / Becker, Robert / Sack, Markus / Cosa Linan, Alejandro / Gerchen, Martin Fungisai / Reinwald, Jonathan Rochus / Oettl, Lars-Lennart / Meyer-Lindenberg, Andreas / Vollmayr, Barbara / Kelsch, Wolfgang / Sartorius, Alexander

    Translational psychiatry

    2018  Volume 8, Issue 1, Page(s) 68

    Abstract: Hyperconnectivity of the default-mode network (DMN) is one of the most widely replicated neuroimaging findings in major depressive disorder (MDD). Further, there is growing evidence for a central role of the lateral habenula (LHb) in the pathophysiology ... ...

    Abstract Hyperconnectivity of the default-mode network (DMN) is one of the most widely replicated neuroimaging findings in major depressive disorder (MDD). Further, there is growing evidence for a central role of the lateral habenula (LHb) in the pathophysiology of MDD. There is preliminary neuroimaging evidence linking LHb and the DMN, but no causal relationship has been shown to date. We combined optogenetics and functional magnetic resonance imaging (fMRI), to establish a causal relationship, using an animal model of treatment-resistant depression, namely Negative Cognitive State rats. First, an inhibitory light-sensitive ion channel was introduced into the LHb by viral transduction. Subsequently, laser stimulation was performed during fMRI acquisition on a 9.4 Tesla animal scanner. Neural activity and connectivity were assessed, before, during and after laser stimulation. We observed a connectivity decrease in the DMN following laser-induced LHb perturbation. Our data indicate a causal link between LHb downregulation and reduction in DMN connectivity. These findings may advance our mechanistic understanding of LHb inhibition, which had previously been identified as a promising therapeutic principle, especially for treatment-resistant depression.
    MeSH term(s) Animals ; Brain/physiopathology ; Brain Mapping ; Depressive Disorder, Treatment-Resistant/physiopathology ; Disease Models, Animal ; Habenula/physiopathology ; Magnetic Resonance Imaging ; Male ; Neural Pathways/physiopathology ; Optogenetics ; Rats
    Language English
    Publishing date 2018-03-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2609311-X
    ISSN 2158-3188 ; 2158-3188
    ISSN (online) 2158-3188
    ISSN 2158-3188
    DOI 10.1038/s41398-018-0121-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Neural Mechanisms of Early-Life Social Stress as a Developmental Risk Factor for Severe Psychiatric Disorders.

    Reinwald, Jonathan Rochus / Becker, Robert / Mallien, Anne Stephanie / Falfan-Melgoza, Claudia / Sack, Markus / Clemm von Hohenberg, Christian / Braun, Urs / Cosa Linan, Alejandro / Gass, Natalia / Vasilescu, Andrei-Nicolae / Tollens, Fabian / Lebhardt, Philipp / Pfeiffer, Natascha / Inta, Dragos / Meyer-Lindenberg, Andreas / Gass, Peter / Sartorius, Alexander / Weber-Fahr, Wolfgang

    Biological psychiatry

    2017  Volume 84, Issue 2, Page(s) 116–128

    Abstract: Background: To explore the domain-general risk factor of early-life social stress in mental illness, rearing rodents in persistent postweaning social isolation has been established as a widely used animal model with translational relevance for ... ...

    Abstract Background: To explore the domain-general risk factor of early-life social stress in mental illness, rearing rodents in persistent postweaning social isolation has been established as a widely used animal model with translational relevance for neurodevelopmental psychiatric disorders such as schizophrenia. Although changes in resting-state brain connectivity are a transdiagnostic key finding in neurodevelopmental diseases, a characterization of imaging correlates elicited by early-life social stress is lacking.
    Methods: We performed resting-state functional magnetic resonance imaging of postweaning social isolation rats (N = 23) 9 weeks after isolation. Addressing well-established transdiagnostic connectivity changes of psychiatric disorders, we focused on altered frontal and posterior connectivity using a seed-based approach. Then, we examined changes in regional network architecture and global topology using graph theoretical analysis.
    Results: Seed-based analyses demonstrated reduced functional connectivity in frontal brain regions and increased functional connectivity in posterior brain regions of postweaning social isolation rats. Graph analyses revealed a shift of the regional architecture, characterized by loss of dominance of frontal regions and emergence of nonfrontal regions, correlating to our behavioral results, and a reduced modularity in isolation-reared rats.
    Conclusions: Our result of functional connectivity alterations in the frontal brain supports previous investigations postulating social neural circuits, including prefrontal brain regions, as key pathways for risk for mental disorders arising through social stressors. We extend this knowledge by demonstrating more widespread changes of brain network organization elicited by early-life social stress, namely a shift of hubness and dysmodularity. Our results highly resemble core alterations in neurodevelopmental psychiatric disorders such as schizophrenia, autism, and attention-deficit/hyperactivity disorder in humans.
    MeSH term(s) Animals ; Behavior, Animal ; Brain/physiopathology ; Conditioning (Psychology) ; Magnetic Resonance Imaging ; Male ; Mental Disorders/physiopathology ; Neural Pathways/physiopathology ; Rats ; Rats, Sprague-Dawley ; Risk Factors ; Social Isolation ; Weaning
    Language English
    Publishing date 2017-12-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209434-4
    ISSN 1873-2402 ; 0006-3223
    ISSN (online) 1873-2402
    ISSN 0006-3223
    DOI 10.1016/j.biopsych.2017.12.010
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 720: 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)
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  6. Article: Neural mechanisms of early-life social stress as a developmental risk factor for severe psychiatric disorders

    Reinwald, Jonathan Rochus / Becker, Robert / Mallien, Anne Stephanie / Falfan-Melgoza, Claudia / Sack, Markus / von Hohenberg, Christian Clemm / Braun, Urs / Linan, Alejandro Cosa / Gass, Natalie / Vasilescu, Andrei-Nicolae / Tollens, Fabian / Lebhardt, Philipp / Pfeiffer, Natascha / Inta, Dragos / Meyer-Lindenberg, Andreas / Gass, Peter / Sartorius, Alexander / Weber-Fahr, Wolfgang

    Biological Psychiatry

    2018  Volume 84, Issue 2, Page(s) 116–128

    Abstract: BACKGROUND: To explore the domain-general risk factor of early-life social stress in mental illness, rearing rodents in persistent postweaning social isolation has been established as a widely used animal model with translational relevance for ... ...

    Abstract BACKGROUND: To explore the domain-general risk factor of early-life social stress in mental illness, rearing rodents in persistent postweaning social isolation has been established as a widely used animal model with translational relevance for neurodevelopmental psychiatric disorders such as schizophrenia. Although changes in resting-state brain connectivity are a transdiagnostic key finding in neurodevelopmental diseases, a characterization of imaging correlates elicited by early-life social stress is lacking. METHODS: We performed resting-state functional magnetic resonance imaging of postweaning social isolation rats (N = 23) 9 weeks after isolation. Addressing well-established transdiagnostic connectivity changes of psychiatric disorders, we focused on altered frontal and posterior connectivity using a seed-based approach. Then, we examined changes in regional network architecture and global topology using graph theoretical analysis. RESULTS: Seed-based analyses demonstrated reduced functional connectivity in frontal brain regions and increased functional connectivity in posterior brain regions of postweaning social isolation rats. Graph analyses revealed a shift of the regional architecture, characterized by loss of dominance of frontal regions and emergence of nonfrontal regions, correlating to our behavioral results, and a reduced modularity in isolation-reared rats. CONCLUSIONS: Our result of functional connectivity alterations in the frontal brain supports previous investigations postulating social neural circuits, including prefrontal brain regions, as key pathways for risk for mental disorders arising through social stressors. We extend this knowledge by demonstrating more widespread changes of brain network organization elicited by early-life social stress, namely a shift of hubness and dysmodularity. Our results highly resemble core alterations in neurodevelopmental psychiatric disorders such as schizophrenia, autism, and attention-deficit/hyperactivity disorder in humans.
    Keywords Animal Models ; Brain Connectivity ; Early Experience ; Frühkindliche Erfahrungen ; Konnektivität (Gehirn) ; Risikofaktoren ; Risk Factors ; Schizophrenia ; Schizophrenie ; Social Isolation ; Social Stress ; Soziale Isolation ; Sozialer Stress ; Tiermodelle
    Language English
    Document type Article
    ZDB-ID 209434-4
    ISSN 1873-2402 ; 0006-3223
    ISSN (online) 1873-2402
    ISSN 0006-3223
    DOI 10.1016/j.biopsych.2017.12.010
    Database PSYNDEX

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 720: 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)

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