Acute effects of hyperglycemia on the peripheral nervous system in zebrafish ( Danio Rerio) following nitroreductase-mediated β-cell ablation.

Acute effects of hyperglycemia on the peripheral nervous system in zebrafish ( Danio Rerio) following nitroreductase-mediated β-cell ablation. Am J Physiol Regul Integr Comp Physiol. 2019 Feb 06;: Authors: Rocker A, Howell J, Voithofer G, Clark JK Abstract Diabetic peripheral neuropathy (DPN) is estimated to affect 50% of diabetic patients. Although highly prevalent, molecular mechanisms remain unknown and treatment is limited to pain relief and glycemic control. Here, we provide a novel model of acute DPN in zebrafish (Danio Rerio)larvae. Beginning 5 days post fertilization (dpf), zebrafish expressing nitroreductase in their pancreatic b-cells were treated with metronidazole (MTZ) for 48 hours and checked for b-cell ablation 7 dpf. In experimental design, this was meant to serve as proof of concept that b-cell ablation and hyperglycemia was possible at this time-point, but surprisingly, we observed changes occurring to both sensory and motor nerve components. Compared to controls, neurod+ sensory neurons were often observed outside of the dorsal root ganglia in MTZ-treated fish. Fewer motor nerves were properly ensheathed by nkx2.2a+perineurial cells and tight junctions were disrupted along the motor nerve in MTZ-treated fish compared to controls. Not surprisingly, the motor axons of the MTZ-treated group were defasciculated compared to the control, myelination was attenuated and there was a subtle difference in Schwann cell number...
Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology - Category: Physiology Authors: Tags: Am J Physiol Regul Integr Comp Physiol Source Type: research