C. elegans detects toxicity of traumatic brain injury generated tau
| العنوان: | C. elegans detects toxicity of traumatic brain injury generated tau |
|---|---|
| المؤلفون: | Luca Russo, Luana Fioriti, Carmina Natale, Elisa R. Zanier, Roberto Chiesa, Luisa Diomede, Maria Monica Barzago, Elena Restelli, Gloria Vegliante, Laura Colombo, Luca Colnaghi, Edoardo Micotti, Margherita Romeo, Ilaria Bertani |
| المصدر: | Neurobiology of Disease, Vol 153, Iss, Pp 105330-(2021) Neurobiology of Disease |
| بيانات النشر: | Elsevier, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Genetically modified mouse, Aβ, amyloid β, Traumatic brain injury, Neuromuscular Junction, Neuromuscular transmission, tau Proteins, Motor Activity, Biology, Article, TBI, traumatic brain injury, lcsh:RC321-571, TauP301L, recombinant tau with the P301L mutation, Mice, 03 medical and health sciences, 0302 clinical medicine, Brain Injuries, Traumatic, medicine, Animals, Neuromuscular synaptic transmission, Cognitive decline, NGM, nematode growth medium, Caenorhabditis elegans, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, p-tau, hyperphosphorylated tau, KO, knockout, PK, proteinase-K, SNAP, simple neuroassessment of asymmetric impairment, Non-Tg, non-transgenic, Neurodegeneration, TBIcontra, tissue from contralateral brain area of TBI mice, Neurodegenerative Diseases, medicine.disease, WT, wild-type, Cell biology, Tauopathy, 030104 developmental biology, Tauopathies, Neurology, Toxicity, tauTBI, TBI-induced abnormal form of tau, TauWT, recombinant wild-type tau, TBIipsi, tissue from ipsilateral brain area of TBI mice, Tau, 030217 neurology & neurosurgery, Contra, contralateral |
| الوصف: | Traumatic brain injury (TBI) is associated with widespread tau pathology in about 30% of patients surviving late after injury. We previously found that TBI in mice induces the formation of an abnormal form of tau (tauTBI) which progressively spreads from the site of injury to remote brain regions. Intracerebral inoculation of TBI brain homogenates into naïve mice induced progressive tau pathology, synaptic loss and late cognitive decline, suggesting a pivotal role of tauTBI in post-TBI neurodegeneration. However, the possibility that tauTBI was a marker of TBI-associated neurodegeneration rather than a toxic driver of functional decline could not be excluded. Here we employed the nematode C. elegans as a biosensor to test the pathogenic role of TBI generated tau. The motility of this nematode depends on efficient neuromuscular transmission and is exceptionally sensitive to the toxicity of amyloidogenic proteins, providing a tractable model for our tests. We found that worms exposed to brain homogenates from chronic but not acute TBI mice, or from mice in which tauTBI had been transmitted by intracerebral inoculation, had impaired motility and neuromuscular synaptic transmission. Results were similar when worms were given brain homogenates from transgenic mice overexpressing tau P301L, a tauopathy mouse model, suggesting that TBI-induced and mutant tau have similar toxic properties. P301L brain homogenate toxicity was similar in wild-type and ptl-1 knock-out worms, indicating that the nematode tau homolog protein PTL-1 was not required to mediate the toxic effect. Harsh protease digestion to eliminate the protein component of the homogenates, pre-incubation with anti-tau antibodies or tau depletion by immunoprecipitation, abolished the toxicity. Homogenates of chronic TBI brains from tau knock-out mice were not toxic to C. elegans, whereas oligomeric recombinant tau was sufficient to impair their motility. This study indicates that tauTBI impairs motor activity and synaptic transmission in C. elegans and supports a pathogenic role of tauTBI in the long-term consequences of TBI. It also sets the groundwork for the development of a C. elegans-based platform for screening anti-tau compounds. Graphical abstract Unlabelled Image Highlights • Traumatic brain injury (TBI) in mice induces a progressive tau pathology. • Brain-injured tissue from chronic but not acute TBI mice impairs C. elegans motility. • TBI tissue immunodepleted of tau or from tau knock-out mice has no toxic effect. • Brain-injured tissue from TBI mice impairs neuromuscular transmission in worms. • C. elegans is a tractable model for investigating tau toxicity generated by TBI. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::241bd53568f58354b57cccba9cff43e8Test http://www.sciencedirect.com/science/article/pii/S0969996121000796Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....241bd53568f58354b57cccba9cff43e8 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |