Are Kynurenine Pathway Alterations Involved in the Locomotor Deterioration in Diabetic Neuropathy?

Background: Diabetes has been declared one of the fastest
growing conditions within the global health emergencies of the
21st century. The effect of prolonged hyperglycemia on the motor
neurons of the ventral horn has been less studied [1] and recently
it has pointed to the kynurenine pathway (KP) as concurrent in the
pathophysiology of Diabetes [2].
Aim: In this work, to continue the exploration of the effects of
prolonged hyperglycemia in the nervous system, we extend the
evaluation to the alterations of KP metabolites as possible factors
in the induction, development and/or chronification of the
diabetic neuropathy.
Method: Using cross sections of lumbar spinal cord in
diabetes type 2 (DT2) -streptozotocin model in Sprague-Dawley
rats. The development of the diabetic neuropathy was demonstrated by hyperglycemia, alterations in the gait pattern and
other test. The KP metabolites were identified by
immunohistochemistry.
Results: The immunofluorescence from KP and concurrent
proinflammatory factors were identified in glia, motor neurons
and non-motor neurons. The induction of KP was confirmed by
the increase in fluorescence of L-kynurenine (L-KYN) possibly also
linked to the inductive augmentation of interferon gamma (IFN-γ)
and tumor necrosis factor alpha (TNF-α). The fluorescence
merging of L-KYN-IFN-γ, L-KYN-TNF-α, quinolinic acid (QUIN) -
advanced glycation end products (AGEs) in DT2 contrasted with
that of the CONTROL (p < 0.05). AGEs was identified in ventral horn
cells as an additional pro-inflammatory factor.
Conclusion: Our results showed divergent metabolic profiles
for glia, motor and non-motor neurons between the CONTROL and
DT2 evaluations. The clusters relating parameters and their
association with the components were distinct by week, type of
cell and study group, thus describing a dynamic process (Figure 1).