Assessment of the tauopathy after spinal cord injury and the effect of immunotherapy on injury complications in central nervous system of male mice

Abstract

Spinal cord injury (SCI) can lead to neurological impairment with significant functional and cognitive deficits. Tau is a microtubule-associated protein, which is highly expressed in neurons, and its abnormalities result in neuronal cell death. Tau protein immunotherapy with specific antibodies can inhibit tau pathology and reduce its complications. Therefore, in this study, the effects of immunotherapy following severe SCI (sSCI) on tau pathologies, locomotor function, memory function, and anxiety behaviors in mouse models were investigated. Methods: Eighteen adult male mice were divided into 3 groups: sham, sSCI(48h), and sSCI(2w); and the amount of cis P-tau was measured in the spinal cord tissue. Then, to evaluate the effect of cis P-tau antibody (cis mAb) on injury complications, 24 adult male mice were divided into 4 groups: sham, sSCI(1M), sSCI(2M)+IgG, and sSCI(2M)+cis mAb. Following treatment, the amount of cis P-tau in brain tissue, structural pathologies of axonal microtubules and mitochondria in the brain and spinal cord tissues, and behavioral changes were assessed. Results: A significant increase in tau pathology was observed in the spinal cord as well as brain areas; confirmed by immunofluorescence and immunoblotting analyses. Moreover, the brain samples were studied by electron microscopy and observed disrupted mitochondria and microtubule structure upon SCI. SCI caused motor dysfunction, memory impairment, and abnormal risk-taking behavior. Importantly, pathogenic cis P-tau elimination with systemic administration of cis mAb restored SCI-related pathological and functional consequences.