Traumatic brain injury derived pathological tau polymorphs induce the distinct propagation pattern and neuroinflammatory response in wild type mice.

Puangmalai, Nicha; Bhatt, Nemil; Bittar, Alice; Jerez, Cynthia; Shchankin, Nikita; Kayed, Rakez

Puangmalai, Nicha; Bhatt, Nemil; Bittar, Alice; Jerez, Cynthia; Shchankin, Nikita; Kayed, Rakez.

Afiliación

Puangmalai N; Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA; Departments of Neurology, Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Bhatt N; Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA; Departments of Neurology, Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Bittar A; Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA; Departments of Neurology, Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Jerez C; Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA; Departments of Neurology, Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Shchankin N; Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA; Departments of Neurology, Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Kayed R; Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA; Departments of Neurology, Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA. Electronic address: rakayed@utmb.edu.

Prog Neurobiol ; 232: 102562, 2024 Jan.

Article en En | MEDLINE | ID: mdl-38135105

ABSTRACT

ABSTRACT

The misfolding and aggregation of the tau protein into neurofibrillary tangles constitutes a central feature of tauopathies. Traumatic brain injury (TBI) has emerged as a potential risk factor, triggering the onset and progression of tauopathies. Our previous research revealed distinct polymorphisms in soluble tau oligomers originating from single versus repetitive mild TBIs. However, the mechanisms orchestrating the dissemination of TBI brain-derived tau polymorphs (TBI-BDTPs) remain elusive. In this study, we explored whether TBI-BDTPs could initiate pathological tau formation, leading to distinct pathogenic trajectories. Wild-type mice were exposed to TBI-BDTPs from sham, single-blast (SB), or repeated-blast (RB) conditions, and their memory function was assessed through behavioral assays at 2- and 8-month post-injection. Our findings revealed that RB-BDTPs induced cognitive and motor deficits, concurrently fostering the emergence of toxic tau aggregates within the injected hippocampus. Strikingly, this tau pathology propagated to cortical layers, intensifying over time. Importantly, RB-BDTP-exposed animals displayed heightened glial cell activation, NLRP3 inflammasome formation, and increased TBI biomarkers, particularly triggering the aggregation of S100B, which is indicative of a neuroinflammatory response. Collectively, our results shed light on the intricate mechanisms underlying TBI-BDTP-induced tau pathology and its association with neuroinflammatory processes. This investigation enhances our understanding of tauopathies and their interplay with neurodegenerative and inflammatory pathways following traumatic brain injury.

Asunto(s)

Lesiones Traumáticas del Encéfalo; Tauopatías; Ratones; Animales; Proteínas tau/metabolismo; Lesiones Traumáticas del Encéfalo/complicaciones; Tauopatías/metabolismo; Ovillos Neurofibrilares/metabolismo; Inflamación/complicaciones; Modelos Animales de Enfermedad

Palabras clave

Neuroinflammatory response; Tau polymorphs; Tau spreading; Traumatic brain injury

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tauopatías / Lesiones Traumáticas del Encéfalo Límite: Animals Idioma: En Revista: Prog Neurobiol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

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