دورية أكاديمية
Determinants of astrocytic pathology in stem cell models of primary tauopathies.
| العنوان: | Determinants of astrocytic pathology in stem cell models of primary tauopathies. |
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| المؤلفون: | Fiock KL; Department of Pathology, University of Iowa, 25 S Grand Ave MRC-108-A, Iowa City, IA, 52240, USA.; Experimental Pathology Graduate Program, University of Iowa, Iowa City, IA, USA.; Carver College of Medicine, University of Iowa, Iowa City, IA, USA., Hook JN; Department of Pathology, University of Iowa, 25 S Grand Ave MRC-108-A, Iowa City, IA, 52240, USA.; Carver College of Medicine, University of Iowa, Iowa City, IA, USA., Hefti MM; Department of Pathology, University of Iowa, 25 S Grand Ave MRC-108-A, Iowa City, IA, 52240, USA. marco-hefti@uiowa.edu.; Experimental Pathology Graduate Program, University of Iowa, Iowa City, IA, USA. marco-hefti@uiowa.edu.; Carver College of Medicine, University of Iowa, Iowa City, IA, USA. marco-hefti@uiowa.edu.; Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA. marco-hefti@uiowa.edu. |
| المصدر: | Acta neuropathologica communications [Acta Neuropathol Commun] 2023 Oct 06; Vol. 11 (1), pp. 161. Date of Electronic Publication: 2023 Oct 06. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: BioMed Central Country of Publication: England NLM ID: 101610673 Publication Model: Electronic Cited Medium: Internet ISSN: 2051-5960 (Electronic) Linking ISSN: 20515960 NLM ISO Abbreviation: Acta Neuropathol Commun Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : BioMed Central, [2013]- |
| مواضيع طبية MeSH: | Tauopathies*/pathology , Supranuclear Palsy, Progressive*/pathology , Chronic Traumatic Encephalopathy*/pathology, Humans ; tau Proteins/genetics ; tau Proteins/metabolism ; Astrocytes/metabolism ; Brain/pathology ; Protein Isoforms/metabolism |
| مستخلص: | 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. (© 2023. BioMed Central Ltd., part of Springer Nature.) |
| التعليقات: | Update of: bioRxiv. 2023 Jul 26;:. (PMID: 37546981) |
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| معلومات مُعتمدة: | K23 NS109284 United States NS NINDS NIH HHS |
| فهرسة مساهمة: | Keywords: Astrocytes; Corticobasal degeneration; Progressive supranuclear palsy; Stem cells; Tau; Tauopathy |
| المشرفين على المادة: | 0 (tau Proteins) 0 (Protein Isoforms) |
| تواريخ الأحداث: | Date Created: 20231006 Date Completed: 20231101 Latest Revision: 20240210 |
| رمز التحديث: | 20240210 |
| مُعرف محوري في PubMed: | PMC10557325 |
| DOI: | 10.1186/s40478-023-01655-1 |
| PMID: | 37803326 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 2051-5960 |
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| DOI: | 10.1186/s40478-023-01655-1 |