Does diabetes mellitus target motor neurons?

Area of Science:

• Neuroscience
• Diabetology
• Cellular Biology

Background:

• Peripheral neurodegeneration is a known complication of chronic diabetes mellitus.
• Clinical evidence suggests sensory neurons are affected before motor neurons.
• Experimental diabetes models show significant sensory neuron loss.

Purpose of the Study:

• To investigate the long-term effects of experimental diabetes on spinal motor neurons.
• To assess the integrity, function, and protein expression in motor neurons of diabetic mice.
• To understand the specific pathological changes in motor neurons during chronic diabetes.

Main Methods:

• Utilized a long-term chronic model of streptozotocin-induced diabetes in mice.
• Examined motor neuron integrity, physiological function, and protein expression over 8 months.
• Analyzed axonal terminals, perikarya, nerve trunk axons, and protein markers (RAGE, PARP, HSP-27, pAKT).

Main Results:

• Motor neurons exhibited progressive distal axonal terminal loss without perikaryal dropout, indicating axon retraction.
• Axon conduction velocity slowed, motor units and neuromuscular junctions were lost, with compensatory enlargement of single motor unit action potentials.
• Elevated expression of stress-related proteins (RAGE, PARP) and neuroprotective proteins (HSP-27, pAKT) was observed in motor neurons.
• Increased Akt mRNA levels were detected in the lumbar spinal cords of diabetic mice.

Conclusions:

• Motor neurons are targeted by diabetes, leading to gradual distal terminal withdrawal rather than cell death.
• Diabetic complications affect motor neuron physiology and molecular pathways, involving both stress and survival responses.
• These findings highlight the specific vulnerability and adaptive mechanisms of motor neurons in chronic diabetic neuropathy.