Abstract
Peripheral sensory diabetic neuropathy is characterized by morphological, electrophysiological
and neurochemical changes to a subpopulation of primary afferent neurons. Here, we
utilized a transgenic mouse model of diabetes (OVE26) and age-matched controls to
histologically examine the effect of chronic hyperglycemia on the activity or abundance
of the enzymes acid phosphatase, cytochrome oxidase and NADPH-diaphorase in primary
sensory neuron perikarya and the dorsal horn of the spinal cord. Quantitative densitometric
characterization of enzyme reaction product revealed significant differences between
diabetic, compared to control, animals for all three enzymes. Levels of acid phosphatase
reaction product were found to be significantly reduced in both small diameter primary
sensory somata and the dorsal horn. Cytochrome oxidase activity was found to be significantly
lower in small primary sensory somata while NADPH-diaphorase labeling was found to
be significantly higher in small primary sensory somata and significantly lower in
the dorsal horn. In addition to these observed biochemical changes, ratiometric analysis
of the number of small versus large diameter primary sensory perikarya in diabetic
and control animals demonstrated a quantifiable decrease in the number of small diameter
cells in the spinal ganglia of diabetic mice. These results suggest that the OVE26
model of diabetes mellitus produces an identifiable disturbance in specific metabolic
pathways of select cells in the sensory nervous system and that this dysfunction may
reflect the progression of a demonstrated cell loss.
