ABSTRACT
Chronic traumatic encephalopathy (CTE) is a distinct neurodegenerative disease that associated with repetitive head trauma. CTE is neuropathologically defined by the perivascular accumulation of abnormally phosphorylated tau protein in the depths of the sulci in the cerebral cortices. In advanced CTE, hyperphosphorylated tau protein deposits are found in widespread regions of brain, however the mechanisms of the progressive neurodegeneration in CTE are not fully understood. In order to identify which proteomic signatures are associated with CTE, we prepared RIPA-soluble fractions and performed quantitative proteomic analysis of postmortem brain tissue from individuals neuropathologically diagnosed with CTE. We found that axonal guidance signaling pathwayrelated proteins were most significantly decreased in CTE. Immunohistochemistry and Western blot analysis showed that axonal signaling pathway-related proteins were down regulated in neurons and oligodendrocytes and neuron-specific cytoskeletal proteins such as TUBB3 and CFL1 were reduced in the neuropils and cell body in CTE. Moreover, oligodendrocyte-specific proteins such as MAG and TUBB4 were decreased in the neuropils in both gray matter and white matter in CTE, which correlated with the degree of axonal injury and degeneration. Our findings indicate that deregulation of axonal guidance proteins in neurons and oligodendrocytes is associated with the neuropathology in CTE. Together, altered axonal guidance proteins may be potential pathological markers for CTE.
Subject(s)
Humans , Axons , Blotting, Western , Brain Injury, Chronic , Brain , Cell Body , Cerebral Cortex , Craniocerebral Trauma , Cytoskeletal Proteins , Gray Matter , Immunohistochemistry , Neurodegenerative Diseases , Neurons , Neuropathology , Neuropil , Oligodendroglia , tau Proteins , White MatterABSTRACT
Objective To observe the effects of treadmill training on the expression of axonal guidance factor Netrin-4 and its receptor deleted in colorectal cancer (DCC) protein in the brains of rats with cerebral ischemia.Also to explore how training promotes the recovery of neurological function after cerebral ischemia.Methods Sixty-three adult, male Sprague-Dawley rats were randomly divided into a sham group (n =9) , a model group (n =27) and an exercise group (n =27).A modified version of Longa's method was used to establish an animal model of cerebral ischemia by occluding the right middle cerebral artery (MCAO) in the rats of the model and exercise groups while the rats of the sham group were subjected to the same surgical procedure except that no thread was inserted.The rats of the exercise group were given treadmill training beginning 24 h after the modeling, while those of the other two groups were left on the treadmill without training.The rats' neurological functioning was tested by assigning modified neurological severity scores (mNSS) on the 3rd, 7th and 14th day after modeling.Then the ischemic brain tissue was dissected to detect the expression of Netrin-4 and DCC protein using western blotting and immunofluorescent staining and analysis.Results On the 3rd, 7th and 14th day after modeling, the model and exercise groups had significant differences in their average mNSS scores when compared to the sham group.The average mNSS scores of the exercise group on the 7th and the 14th day were significantly lower than those of the model group at the same time point.The average expression level of Netrin-4 and DCC protein in the exercise group was significantly higher in than the model group on the 7th and 14 th days.Immunofluorescent staining showed that Netrin-4 was mainly observed in the blood vessels and astrocytes in the ischemic brain area.DCC protein was found mainly in neural processes and astrocytes in the same area.Conclusions Treadmill training can improve the recovery of neurological function after cerebral ischemia.Its mechanisms may be partly attributed to up-regulating the expression of Netrin-4 and DCC protein in the ischemic brain area, which strengthens the regeneration and reconstruction of nerves and blood vessels.