Transcriptional Profiling in a Novel Swine Model of Traumatic Brain Injury

Shin, Samuel S.; Gottschalk, Amy C.; Mazandi, Vanessa; Kilbaugh, Todd J.; Hefti, Marco M.

doi:10.1089/neur.2021.0051

Cited by 4 publications

(3 citation statements)

References 43 publications

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“…RNA extraction and sequencing were done by GeneWhiz’s sequencing facility on a fee-for-service basis. Data analysis was conducted as previously described [ 28 ]. Briefly, RNA sequencing reads were aligned to the hg38 human reference genome using STAR aligner.…”

Section: Methodsmentioning

confidence: 99%

Determinants of astrocytic pathology in stem cell models of primary tauopathies

Fiock,

Hook,

Hefti

2023

acta neuropathol commun

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Astrocytic tau aggregates are seen in several primary and secondary tauopathies, including progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and chronic traumatic encephalopathy (CTE). In all of these diseases, astrocytic tau consists mostly of the longer (4R) tau isoform, even when adjacent neuronal aggregates consist of a mixture of 3- and 4R tau, as in CTE. Even the rare astrocytic tau aggregates seen in Pick’s disease appear to contain both 3R and 4R tau. The reasons for this, and the mechanisms by which astrocytic tau aggregates form, remain unclear. We used a combination of RNA in situ hybridization and immunofluorescence in post-mortem human brain tissue, as well as tau uptake studies in human stem cell-derived astrocytes, to determine the origins of astrocytic tau in 4R tauopathies. We found no differences in tau mRNA expression between diseases or between tau positive and negative astrocytes within PSP. We then found that stem cell-derived astrocytes preferentially take up long isoform (4R) recombinant tau and that this uptake is impaired by induction of reactivity with inflammatory stimuli or nutritional stress. Astrocytes exposed to either 3R or 4R tau also showed downregulation of genes related to astrocyte differentiation. Our findings suggest that astrocytes preferentially take up neuronal 4R tau from the extracellular space, potentially explaining why 4R tau is the predominant isoform in astrocytic tau aggregates.

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Section: Methodsmentioning

confidence: 99%

Determinants of astrocytic pathology in stem cell models of primary tauopathies

Fiock,

Hook,

Hefti

2023

acta neuropathol commun

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“…Craniotomy-based models primarily mimic open-head injuries such as impalement or gunshot wounds, which may not fully capture the complexities and mechanisms of closed-head injuries, as the CCI is typically conducted with the pig’s head secured in a stereotaxic frame, not allowing for any movement of the head during impact. Nevertheless, studies using the CCI to induce TBI have led to crucial understanding on primary and secondary injury mechanisms [ 67 , 68 ].…”

Section: Reviewmentioning

confidence: 99%

The Pig as a Translational Animal Model for Biobehavioral and Neurotrauma Research

Netzley

Pelled

2023

Biomedicines

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In recent decades, the pig has attracted considerable attention as an important intermediary model animal in translational biobehavioral research due to major similarities between pig and human neuroanatomy, physiology, and behavior. As a result, there is growing interest in using pigs to model many human neurological conditions and injuries. Pigs are highly intelligent and are capable of performing a wide range of behaviors, which can provide valuable insight into the effects of various neurological disease states. One area in which the pig has emerged as a particularly relevant model species is in the realm of neurotrauma research. Indeed, the number of investigators developing injury models and assessing treatment options in pigs is ever-expanding. In this review, we examine the use of pigs for cognitive and behavioral research as well as some commonly used physiological assessment methods. We also discuss the current usage of pigs as a model for the study of traumatic brain injury. We conclude that the pig is a valuable animal species for studying cognition and the physiological effect of disease, and it has the potential to contribute to the development of new treatments and therapies for human neurological and psychiatric disorders.

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“…RNA extraction and sequencing were done by GeneWhiz's sequencing facility on a fee-for-service basis. Data analysis was conducted as previously described (Shin et al, 2022). Briefly, RNA sequencing reads were aligned to the hg38 human reference genome using STAR aligner.…”

Section: Rna Sequencingmentioning

confidence: 99%

Determinants of Astrocytic Pathology in Stem Cell Models of Primary Tauopathies

Fiock

Hook

Hefti

2023

Preprint

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Introduction: Astrocytic tau aggregates are seen in several primary and secondary tauopathies, including progressive supranuclear palsy, corticobasal degeneration, and chronic traumatic encephalopathy. In all cases, astrocytic tau consists exclusively of the longer (4R) tau isoform, even when adjacent neuronal aggregates consist of a mixture of 3- and 4R tau, as in chronic traumatic encephalopathy. The reasons for this and the mechanisms by which astrocytic tau aggregates form remain unclear. Methods: We used a combination of RNA in situ hybridization and immunofluorescence in human post-mortem brain tissue and tau uptake studies in human stem-cell-derived astrocytes to determine the origins of astrocytic tau in 4R tauopathies. Results: We found that astrocytes in 4R tauopathies do not upregulate tau mRNA expression, either comparing all astrocytes between disease or tau positive- and negative astrocytes within diseases. We then found that stem-cell-derived astrocytes preferentially take up long isoform (4R) labeled recombinant tau and that this uptake is impaired by inflammation or nutritional stress. Astrocytes exposed to either 3R or 4R tau also showed downregulation of genes related to astrocyte differentiation. Discussion: Our findings suggest that astrocytes preferentially take up neuronal 4R tau from the extracellular space, which potentially explains why astrocytic tau aggregates contain only 4R tau, and that tau uptake is impaired by decreased nutrient availability or neuroinflammation, both of which are common in the aging brain.

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Transcriptional Profiling in a Novel Swine Model of Traumatic Brain Injury

Cited by 4 publications

References 43 publications

Determinants of astrocytic pathology in stem cell models of primary tauopathies

Determinants of astrocytic pathology in stem cell models of primary tauopathies

The Pig as a Translational Animal Model for Biobehavioral and Neurotrauma Research

Determinants of Astrocytic Pathology in Stem Cell Models of Primary Tauopathies

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