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  1. Article ; Online: Association between single moderate to severe traumatic brain injury and long-term tauopathy in humans and preclinical animal models: a systematic narrative review of the literature.

    Walker, Ariel / Chapin, Ben / Abisambra, Jose / DeKosky, Steven T

    Acta neuropathologica communications

    2022  Volume 10, Issue 1, Page(s) 13

    Abstract: Background: The initiation, anatomic pattern, and extent of tau spread in traumatic brain injury (TBI), and the mechanism by which TBI leads to long-term tau pathology, remain controversial. Some studies suggest that moderate to severe TBI is sufficient ...

    Abstract Background: The initiation, anatomic pattern, and extent of tau spread in traumatic brain injury (TBI), and the mechanism by which TBI leads to long-term tau pathology, remain controversial. Some studies suggest that moderate to severe TBI is sufficient to promote tau pathology; however, others suggest that it is simply a consequence of aging. We therefore conducted a systematic narrative review of the literature addressing whether a single moderate to severe head injury leads to long-term development of tauopathy in both humans and animal models.
    Methods: Studies considered for inclusion in this review assessed a single moderate to severe TBI, assessed tau pathology at long-term timepoints post-injury, comprised experimental or observational studies, and were peer-reviewed and published in English. Databases searched included: PUBMED, NCBI-PMC, EMBASE, Web of Science, Academic Search Premiere, and APA Psychnet. Search results were uploaded to Covidence®, duplicates were removed, and articles underwent an abstract and full-text screening process. Data were then extracted and articles assessed for risk of bias.
    Findings: Of 4,150 studies screened, 26 were eligible for inclusion, of which 17 were human studies, 8 were preclinical animal studies, and 1 included both human and preclinical animal studies. Most studies had low to moderate risk of bias. Most human and animal studies (n = 12 and 9, respectively) suggested that a single moderate to severe TBI resulted in greater development of long-term tauopathy compared to no history of head injury. This conclusion should be interpreted with caution, however, due to several limitations: small sample sizes; inconsistencies in controlling for confounding factors that may have affected tau pathology (e.g., family history of dementia or neurological illnesses, apolipoprotein E genotype, etc.), inclusion of mostly males, and variation in reporting injury parameters.
    Interpretation: Results indicate that a single moderate to severe TBI leads to greater chronic development of tauopathy compared to no history of head injury. This implies that tau pathology induced may not be transient, but can progressively develop over time in both humans and animal models. Targeting these tau changes for therapeutic intervention should be further explored to elucidate if disease progression can be reversed or mitigated.
    MeSH term(s) Animals ; Brain/pathology ; Brain Injuries, Traumatic/complications ; Brain Injuries, Traumatic/pathology ; Disease Models, Animal ; Humans ; Tauopathies/etiology ; Tauopathies/pathology
    Language English
    Publishing date 2022-01-31
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Systematic Review
    ZDB-ID 2715589-4
    ISSN 2051-5960 ; 2051-5960
    ISSN (online) 2051-5960
    ISSN 2051-5960
    DOI 10.1186/s40478-022-01311-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Targeted brain-specific tauopathy compromises peripheral skeletal muscle integrity and function.

    Alava, Bryan / Hery, Gabriela / Sidhom, Silvana / Prokop, Stefan / Esser, Karyn / Abisambra, Jose

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Tauopathies are neurodegenerative disorders in which the pathological intracellular aggregation of the protein tau causes cognitive deficits. Additionally, clinical studies report muscle weakness in populations with tauopathy. However, whether neuronal ... ...

    Abstract Tauopathies are neurodegenerative disorders in which the pathological intracellular aggregation of the protein tau causes cognitive deficits. Additionally, clinical studies report muscle weakness in populations with tauopathy. However, whether neuronal pathological tau species confer muscle weakness, and whether skeletal muscle maintains contractile capacity in primary tauopathy remains unknown. Here, we identified skeletal muscle abnormalities in a mouse model of primary tauopathy, expressing human mutant P301L-tau using adeno-associated virus serotype 8 (AAV8). AAV8-P301L mice showed grip strength deficits, hyperactivity, and abnormal histological features of skeletal muscle. Additionally, spatially resolved gene expression of muscle cross sections were altered in AAV8-P301L myofibers. Transcriptional changes showed alterations of genes encoding sarcomeric proteins, proposing a weakness phenotype. Strikingly, specific force of the soleus muscle was blunted in AAV8-P301L tau male mice. Our findings suggest tauopathy has peripheral consequences in skeletal muscle that contribute to weakness in tauopathy.
    Language English
    Publishing date 2023-11-17
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.11.17.567586
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Targeted brain-specific tauopathy compromises peripheral skeletal muscle integrity and function.

    Alava, Bryan / Hery, Gabriela / Sidhom, Silvana / Gutierrez-Monreal, Miguel / Prokop, Stefan / Esser, Karyn A / Abisambra, Jose

    Aging brain

    2024  Volume 5, Page(s) 100110

    Abstract: Tauopathies are neurodegenerative disorders in which the pathological intracellular aggregation of the protein tau causes cognitive deficits. Additionally, clinical studies report muscle weakness in populations with tauopathy. However, whether neuronal ... ...

    Abstract Tauopathies are neurodegenerative disorders in which the pathological intracellular aggregation of the protein tau causes cognitive deficits. Additionally, clinical studies report muscle weakness in populations with tauopathy. However, whether neuronal pathological tau species confer muscle weakness, and whether skeletal muscle maintains contractile capacity in primary tauopathy remains unknown. Here, we identified skeletal muscle abnormalities in a mouse model of primary tauopathy, expressing human mutant P301L-tau using adeno-associated virus serotype 8 (AAV8). AAV8-P301L mice showed grip strength deficits, hyperactivity, and abnormal histological features of skeletal muscle. Additionally, spatially resolved gene expression of muscle cross sections were altered in AAV8-P301L myofibers. Transcriptional changes showed alterations of genes encoding sarcomeric proteins, proposing a weakness phenotype. Strikingly, specific force of the soleus muscle was blunted in AAV8-P301L tau male mice. Our findings suggest tauopathy has peripheral consequences in skeletal muscle that contribute to weakness in tauopathy.
    Language English
    Publishing date 2024-02-24
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2589-9589
    ISSN (online) 2589-9589
    DOI 10.1016/j.nbas.2024.100110
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Tau-mediated dysregulation of RNA: Evidence for a common molecular mechanism of toxicity in frontotemporal dementia and other tauopathies.

    Koren, Shon A / Galvis-Escobar, Sara / Abisambra, Jose F

    Neurobiology of disease

    2020  Volume 141, Page(s) 104939

    Abstract: Frontotemporal dementias (FTDs) encompass several disorders commonly characterized by progressive frontotemporal lobar degeneration and dementia. Pathologically, TDP-43, FUS, dipeptide repeats, and tau constitute the protein aggregates in FTD, which in ... ...

    Abstract Frontotemporal dementias (FTDs) encompass several disorders commonly characterized by progressive frontotemporal lobar degeneration and dementia. Pathologically, TDP-43, FUS, dipeptide repeats, and tau constitute the protein aggregates in FTD, which in turn coincide with heterogeneity in clinical variants. The underlying molecular etiology explaining the formation of each type of protein aggregate remains unclear; however, dysregulated RNA metabolism rises as a common pathogenic factor. Alongside with TDP-43 and FUS, which bind to and regulate RNA dynamics, emerging data suggest that tau may also regulate RNA metabolism and translation. The complex mechanisms that drive translational selectivity in turn regulate the broad clinical presentation of FTDs. Here, we focus on the enigmatic relationship between tau and RNA and review the mechanisms of tau-mediated dysregulation of RNA in tauopathies such as FTD.
    MeSH term(s) Animals ; Brain/metabolism ; Brain/pathology ; Frontotemporal Dementia/metabolism ; Frontotemporal Dementia/pathology ; Humans ; Protein Aggregation, Pathological/metabolism ; RNA/metabolism ; Tauopathies/metabolism ; Tauopathies/pathology ; tau Proteins/metabolism
    Chemical Substances tau Proteins ; RNA (63231-63-0)
    Language English
    Publishing date 2020-05-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1211786-9
    ISSN 1095-953X ; 0969-9961
    ISSN (online) 1095-953X
    ISSN 0969-9961
    DOI 10.1016/j.nbd.2020.104939
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Effects of altered tau expression on dentate granule cell excitability in mice.

    Cloyd, Ryan A / Koren, John / Abisambra, Jose F / Smith, Bret N

    Experimental neurology

    2021  Volume 343, Page(s) 113766

    Abstract: Tauopathies, including Alzheimer's disease, are characterized by progressive accumulation of hyperphosphorylated and pathologic tau protein in association with onset of cognitive and behavioral impairment. Tau pathology is also associated with increased ... ...

    Abstract Tauopathies, including Alzheimer's disease, are characterized by progressive accumulation of hyperphosphorylated and pathologic tau protein in association with onset of cognitive and behavioral impairment. Tau pathology is also associated with increased susceptibility to seizures and epilepsy, with tau
    MeSH term(s) Age Factors ; Animals ; Dentate Gyrus/cytology ; Dentate Gyrus/metabolism ; Excitatory Postsynaptic Potentials/physiology ; Female ; Gene Expression ; Humans ; Male ; Membrane Potentials/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Organ Culture Techniques ; tau Proteins/biosynthesis ; tau Proteins/genetics
    Chemical Substances Mapt protein, mouse ; tau Proteins
    Language English
    Publishing date 2021-05-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 207148-4
    ISSN 1090-2430 ; 0014-4886
    ISSN (online) 1090-2430
    ISSN 0014-4886
    DOI 10.1016/j.expneurol.2021.113766
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Age dictates brain functional connectivity and axonal integrity following repetitive mild traumatic brain injuries.

    Criado-Marrero, Marangelie / Ravi, Sakthivel / Bhaskar, Ekta / Barroso, Daylin / Pizzi, Michael A / Williams, Lakiesha / Wellington, Cheryl L / Febo, Marcelo / Abisambra, Jose Francisco

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Traumatic brain injuries (TBI) present a major public health challenge, demanding an in-depth understanding of age-specific signs and vulnerabilities. Aging not only significantly influences brain function and plasticity but also elevates the risk of ... ...

    Abstract Traumatic brain injuries (TBI) present a major public health challenge, demanding an in-depth understanding of age-specific signs and vulnerabilities. Aging not only significantly influences brain function and plasticity but also elevates the risk of hospitalizations and death following repetitive mild traumatic brain injuries (rmTBIs). In this study, we investigate the impact of age on brain network changes and white matter properties following rmTBI employing a multi-modal approach that integrates resting-state functional magnetic resonance imaging (rsfMRI), graph theory analysis, diffusion tensor imaging (DTI), and Neurite Orientation Dispersion and Density Imaging (NODDI). Utilizing the CHIMERA model, we conducted rmTBIs or sham (control) procedures on young (2.5-3 months old) and aged (22-month-old) male and female mice to model high risk groups. Functional and structural imaging unveiled age-related reductions in communication efficiency between brain regions, while injuries induced opposing effects on the small-world index across age groups, influencing network segregation. Functional connectivity analysis also identified alterations in 79 out of 148 brain regions by age, treatment (sham vs. rmTBI), or their interaction. Injuries exerted pronounced effects on sensory integration areas, including insular and motor cortices. Age-related disruptions in white matter integrity were observed, indicating alterations in various diffusion directions (mean, radial, axial diffusivity, fractional anisotropy) and density neurite properties (dispersion index, intracellular and isotropic volume fraction). Inflammation, assessed through Iba-1 and GFAP markers, correlated with higher dispersion in the optic tract, suggesting a neuroinflammatory response in aged animals. These findings provide a comprehensive understanding of the intricate interplay between age, injuries, and brain connectivity, shedding light on the long-term consequences of rmTBIs.
    Language English
    Publishing date 2024-01-26
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.01.25.577316
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Microsome Isolation from Tissue.

    Bodero, Maria / Francisco Abisambra, Jose

    Bio-protocol

    2016  Volume 4, Issue 3

    Abstract: This protocol details the extraction of microsomes from frozen tissue in order to further examine the protein-protein interactions occurring within the endoplasmic reticulum. This protocol was adapted from ... ...

    Abstract This protocol details the extraction of microsomes from frozen tissue in order to further examine the protein-protein interactions occurring within the endoplasmic reticulum. This protocol was adapted from Abisambra
    Language English
    Publishing date 2016-07-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2833269-6
    ISSN 2331-8325
    ISSN 2331-8325
    DOI 10.21769/bioprotoc.1038
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Manganese-Enhanced Magnetic Resonance Imaging: Overview and Central Nervous System Applications With a Focus on Neurodegeneration.

    Cloyd, Ryan A / Koren, Shon A / Abisambra, Jose F

    Frontiers in aging neuroscience

    2018  Volume 10, Page(s) 403

    Abstract: Manganese-enhanced magnetic resonance imaging (MEMRI) rose to prominence in the 1990s as a sensitive approach to high contrast imaging. Following the discovery of manganese conductance through calcium-permeable channels, MEMRI applications expanded to ... ...

    Abstract Manganese-enhanced magnetic resonance imaging (MEMRI) rose to prominence in the 1990s as a sensitive approach to high contrast imaging. Following the discovery of manganese conductance through calcium-permeable channels, MEMRI applications expanded to include functional imaging in the central nervous system (CNS) and other body systems. MEMRI has since been employed in the investigation of physiology in many animal models and in humans. Here, we review historical perspectives that follow the evolution of applied MRI research into MEMRI with particular focus on its potential toxicity. Furthermore, we discuss the more current
    Language English
    Publishing date 2018-12-13
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2558898-9
    ISSN 1663-4365
    ISSN 1663-4365
    DOI 10.3389/fnagi.2018.00403
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Brain injury in the context of tauopathies.

    Abisambra, Jose F / Scheff, Stephen

    Journal of Alzheimer's disease : JAD

    2014  Volume 40, Issue 3, Page(s) 495–518

    Abstract: Traumatic brain injury (TBI) is the most common form of head injury and is a leading cause of death worldwide. Due to the vast variability in the types and severity of trauma, the cellular consequences of head injury are not completely understood. The ... ...

    Abstract Traumatic brain injury (TBI) is the most common form of head injury and is a leading cause of death worldwide. Due to the vast variability in the types and severity of trauma, the cellular consequences of head injury are not completely understood. The development of reliable models of TBI will aid in understanding the molecular consequences of head trauma, and they will assist in identifying biological surrogate markers of the degree of damage and prognosis. In doing so, effective therapeutic strategies can be applied. Current in vivo experimental models yield important information, but they too have a significant amount of variation. The goal of this review is to re-evaluate the use of these in vivo models of TBI and assess whether they correlate with the consequence of TBI in humans from the perspective of tau, an axonal microtubule-stabilizing protein. We present and discuss the current models of traumatic head injury, and we focus on those that assess changes in tau. We evaluate reports of TBI in humans that measured changes in tau and that were detectable in serum and cerebrospinal fluid, and as a pathological consequence in brain tissue.
    MeSH term(s) Animals ; Brain/metabolism ; Brain/pathology ; Brain Injuries/blood ; Brain Injuries/cerebrospinal fluid ; Brain Injuries/complications ; Brain Injuries/pathology ; Disease Models, Animal ; Humans ; Tauopathies/etiology ; tau Proteins/blood ; tau Proteins/cerebrospinal fluid
    Chemical Substances tau Proteins
    Language English
    Publishing date 2014
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 1440127-7
    ISSN 1875-8908 ; 1387-2877
    ISSN (online) 1875-8908
    ISSN 1387-2877
    DOI 10.3233/JAD-131019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: A new opportunity for MEMRI.

    Cloyd, Ryan / Vandsburger, Moriel / Abisambra, Jose F

    Aging

    2017  Volume 9, Issue 8, Page(s) 1855–1856

    MeSH term(s) Animals ; Chlorides/administration & dosage ; Chlorides/adverse effects ; Contrast Media/administration & dosage ; Contrast Media/adverse effects ; Edetic Acid/administration & dosage ; Edetic Acid/analogs & derivatives ; Edetic Acid/therapeutic use ; Humans ; Magnetic Resonance Imaging/methods ; Manganese Compounds/administration & dosage ; Manganese Compounds/adverse effects ; Mice, Transgenic ; Neurodegenerative Diseases/diagnostic imaging ; Pyridoxal Phosphate/administration & dosage ; Pyridoxal Phosphate/analogs & derivatives ; Pyridoxal Phosphate/therapeutic use
    Chemical Substances Chlorides ; Contrast Media ; Manganese Compounds ; Pyridoxal Phosphate (5V5IOJ8338) ; Edetic Acid (9G34HU7RV0) ; N,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acid (P28BIW0UTB) ; manganese chloride (QQE170PANO)
    Language English
    Publishing date 2017-09-12
    Publishing country United States
    Document type Editorial
    ISSN 1945-4589
    ISSN (online) 1945-4589
    DOI 10.18632/aging.101283
    Database MEDical Literature Analysis and Retrieval System OnLINE

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