Diabetic neuropathy has no treatment but this in viro study demonstrates that there is perhaps hope with mitochondrion fusion drugs or fission inhibitors as PBT434 ( by eliminating iron overload causing fission). Long way to human studies but promising when there is better understanding about the pathogenesis.
Spine (Phila Pa 1976). 2018 Dec 21. doi: 10.1097/BRS.0000000000002952. [Epub ahead of print]High-glucose-induced Mitochondrial Dynamics Disorder of Spinal Cord Neurons in Diabetic Rats and Its Effect on Mitochondrial Spatial Distribution.
Abstract
STUDY DESIGN:
A randomized, double-blind, controlled trial.
OBJECTIVE:
Few studies have investigated the changes in mitochondrial dynamics in spinal cord neurons. Meanwhile, the distribution of mitochondria in axons remains unclear.In the present study, the investigators attempted to clarify these questions, and focused in observing the changes in mitochondrial spatial distribution under a high-glucose environment.
SUMMARY OF BACKGROUND DATA:
Mitochondrial dynamics disorder is one of the main mechanisms that lead to nervous system diseases due to its adverse effects on mitochondrial morphology, function and axon distribution. High-glucose stress can promote the increase in mitochondrial fission of various types of cells.
METHODS:
The lumbar spinal cord of type 1 diabetic Sprague-Dawley rats at four weeks was observed. VSC4.1 cells were cultured, and divided in to three groups: normal control group, high-glucose intervention group, and high-glucose intervention combined with mitochondrial fission inhibitor Mdivi-1 intervention group. Immunohistochemistry and immunofluorescence methods were used to detect the expression of mitochondrial marker VDAC-1 in the spinal cord. An electron microscope was used to observe the number, structure and distribution of mitochondria. Western blot was used to detect VDAC-1, fusion protein MFN1, MFN2 and OPA1, and fission protein FIS1 and DRP1. Living cell mitochondrial staining was performed using MitoTracker. Laser confocal microscopy and an Olympus live cell workstation were used to observe the mitochondrial changes.
RESULTS:
The mitochondrial dynamics of spinal cord-related neurons under an acute high glucose environment were significantly unbalanced, including a reduction of fusion and increase of fission. Hence, mitochondrial fission has the absolute advantage. The total number of mitochondria in neuronal axons significantly decreased.
CONCLUSION:
Increased mitochondrial fission and abnormal distribution occurred in spinal cord-related neurons in a high-glucose environment. Mdivi-1 could significantly improve these disorders of mitochondria in VSC4.1 cells. Mitochondrial division inhibitors had a positive significance on diabetic neuropathy.
