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Spinal Cord Injury and Tau Pathology in the Central Nervous System
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Elnaz Nakhjiri   , Parviz Shahabi |
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Abstract: (236 Views) |
Introduction: Spinal cord injury (SCI) can lead to neurological impairment with significant functional and cognitive deficits. It is well established that SCI results in neurodegeneration that gradually spreads to other cord areas. Tau is a microtubule-associated protein abundant in neurons and whose abnormalities result in neuronal cell death. Tau immunotherapy with specific antibodies can inhibit tau pathology and reduces its complications. Therefore, in this study, the effects of immunotherapy following severe SCI on tau pathology, locomotor function, spatial memory, and anxiety behaviors in mouse models were investigated.
Methods and Materials: A total of 54 adult male mice were assigned to six groups (n=9): Sham (laminectomy without injury), sSCI (48h), sSCI (2W), sSCI (1M) (severe compression injury at the T8 segment of the spinal cord and sacrificed 48 h, two weeks, and one month after the SCI), sSCI (2M)+IgG (severe compression injury at T8 and received IgG for two months), and sSCI (2M)+cis mAb (severe compression injury at T8 and received cis P-tau monoclonal antibody for two months). Following treatment, the amount of cis P-tau, structural pathologies of axonal microtubules and mitochondria in the brain and spinal cord tissues, and behavioral changes were assessed.
Results: Immunostaining and immunoblotting confirmed a progressive increase in tau pathology in the spinal cord and brain areas. Moreover, we used electron microscopy to examine brain samples and observed disrupted mitochondria and microtubule structures following SCI. SCI resulted in motor dysfunction, memory impairment, and abnormal risk-taking behavior. Notably, eliminating pathogenic cis P-tau via systemic administration of appropriate monoclonal antibodies restored SCI’s pathological and functional consequences.
Conclusion: Our findings suggest that SCI causes severe tauopathy that spreads to brain areas, indicating brain dysfunction. Additionally, tau immunotherapy with an anti-cis P-tau antibody could suppress pathogenic outcomes in SCI mouse models, with significant clinical implications for SCI patients. |
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| Keywords: Spinal cord injury, Cis P-tau, Traumatic brain injury, Monoclonal antibody, Cognitive decline |
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Full-Text [PDF 324 kb]
(28 Downloads)
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Type of Study: Research |
Subject:
General
Received: 2024/02/12 | Accepted: 2023/08/23 | Published: 2023/08/23
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