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Macroautophagy is inhibited in human patients with degenerative cervical myelopathy
EANS Academy. Smith S. 09/26/19; 275959; EP02063
Sam Smith
Sam Smith

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Abstract
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Background: Degenerative cervical myelopathy (DCM) is a progressive degenerative disease that is the most common cause of spinal cord injury in the older population. Macroutophagy is a conserved cellular process that causes the lysosomal degradation of cytoplasmic contents and is disrupted in many neurodegenerative diseases. We aimed to investigate the involvement of autophagy in the pathogenesis of DCM.
Methods: Retrospective immunohistochemical analysis on spinal cord tissue from 7 human cases of DCM and 5 healthy controls. Spinal cord sections were immunohistochemically stained using antibodies against proteins involved in autophagy, imaged using an Axio Imager Z2 and analysed with ImageJ. Results were statistically analysed using Graphpad Prism 6.
Results: We found gross deformity of cases compared to controls with a significant reduction in large (over 101mm2) NeuN positive cells. All cases showed significantly reduced numbers of LC3 puncta. Consistent with reduced macroautophagy, large p62 aggregates were present in 4/7 cases and 0/5 controls. Tau and beta-amyloid staining was sparse but was elevated in some cases. Lamp2 was unaltered in DCM but Bcl-2 was significantly increased in cases. Bcl-2 and p62 staining was significantly higher in severe cases of DCM compared to mild cases. We found a weak correlation between p62 and bcl-2 expression.
Conclusions: We conclude that macroautophagy is inhibited in the spinal cord grey matter in DCM; the degree of inhibition correlates with clinical severity. Macroautophagy may normally protect against neuronal death in DCM. Stimulation of macroautophagy may be a therapeutic target in DCM to delay development and progression of myelopathy.
Background: Degenerative cervical myelopathy (DCM) is a progressive degenerative disease that is the most common cause of spinal cord injury in the older population. Macroutophagy is a conserved cellular process that causes the lysosomal degradation of cytoplasmic contents and is disrupted in many neurodegenerative diseases. We aimed to investigate the involvement of autophagy in the pathogenesis of DCM.
Methods: Retrospective immunohistochemical analysis on spinal cord tissue from 7 human cases of DCM and 5 healthy controls. Spinal cord sections were immunohistochemically stained using antibodies against proteins involved in autophagy, imaged using an Axio Imager Z2 and analysed with ImageJ. Results were statistically analysed using Graphpad Prism 6.
Results: We found gross deformity of cases compared to controls with a significant reduction in large (over 101mm2) NeuN positive cells. All cases showed significantly reduced numbers of LC3 puncta. Consistent with reduced macroautophagy, large p62 aggregates were present in 4/7 cases and 0/5 controls. Tau and beta-amyloid staining was sparse but was elevated in some cases. Lamp2 was unaltered in DCM but Bcl-2 was significantly increased in cases. Bcl-2 and p62 staining was significantly higher in severe cases of DCM compared to mild cases. We found a weak correlation between p62 and bcl-2 expression.
Conclusions: We conclude that macroautophagy is inhibited in the spinal cord grey matter in DCM; the degree of inhibition correlates with clinical severity. Macroautophagy may normally protect against neuronal death in DCM. Stimulation of macroautophagy may be a therapeutic target in DCM to delay development and progression of myelopathy.
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