Abstract
To analyse the contributions of metabolic toxicity of high glucose level and accompanying
hyperosmolality to the development of diabetic neuropathy, mouse dorsal root ganglion
(DRG) cultures were used. DRGs from postnatal day 7 mice were embedded in collagen
gel and incubated in RPMI 1640 culture medium with increasing concentrations of glucose
or equimolar amounts of mannitol which would create similar osmolalities. Outgrowth
of axons from the peripheral nerve attached to DRG and migration of cells into the
gel were quantified. The extent of cell death, apoptosis and mitosis among the migrating
cells and apoptosis among DRG neurons following exposure to high glucose or mannitol
were also evaluated. The growth of axons was almost equally affected by increasing
concentrations of glucose or mannitol up to 395 mOsm/kg H2 O. Number of migrating cells was close to control values with mannitol between 340–395 mOsm/kg
H2 O while high concentrations of glucose always decreased it. Exposure to high glucose
or mannitol led to increased proportions of dead and apoptotic migrating cells and
apoptotic DRG neurons. Mitotic activity was also negatively affected by high glucose
or mannitol. While glucose proved significantly more detrimental to migrating cells
than mannitol in the latter tests, the extent of apoptosis was similar among DRG neurons
in both conditions. In conclusion, the contribution of hyperosmolality to the development
of neuropathy in high glucose condition appears to be quite significant. The peripheral
nerve cells and neurons, however, are differentially affected by hyperosmolality and
metabolic toxicity of high glucose.
Key words
diabetic neuropathy - dorsal root ganglion - high glucose - hyperosmolality - mannitol
References
Correspondence
drgurkan@yyu.edu.tr
