Paclitaxel (PTX)-induced peripheral neuropathy (PIPN)
is a debilitating
health condition which is a result of degeneration of peripheral nerves
found in extremities. Currently, there are no established treatment
methods that can prevent or protect from PIPN. Fluocinolone acetonide
(FA) has been recently identified as a potential candidate for protection
from PIPN. However, the fundamental mechanism of action is still unknown.
In this study, we showed that enhanced anterograde mitochondrial movement
in dorsal root ganglion (DRG) cells has a major role in FA-mediated
neuroprotection in PIPN. In this study, cells were treated with PTX
or FA along with their combination followed by mitochondrial fluorescence
staining. Somal (proximal) and axonal (distal) mitochondria were selectively
stained using a microfluidic compartmentalized chamber with different
MitoTrackers blue and red, respectively, which we termed, the two-color
staining approach. Results revealed that axons were protected from
degeneration by the PTX effect when treated along with FA. PTX exposure
alone resulted in low mitochondrial mobility in DRG cells. However,
cotreatment with PTX and FA showed significant enhancement of anterograde
trafficking of somal (proximal) mitochondria to distal axons. Similarly,
cotreatment with FA restored mitochondrial mobility significantly.
Overall, this study affirms that increasing mitochondrial recruitment
into the axon by cotreatment with FA can be a worthwhile strategy
to protect or prevent PIPN. The proposed two-color staining approach
can be extended to study trafficking for other neuron-specific subcellular
organelles.