RNA-Binding Proteins HuB, HuC, and HuD are Distinctly Regulated in Dorsal Root Ganglia Neurons from STZ-Sensitive Compared to STZ-Resistant Diabetic Mice

Abstract

The neuron-specific Elav-like Hu RNA-binding proteins were described to play an important role in neuronal differentiation and plasticity by ensuring the post-transcriptional control of RNAs encoding for various proteins. Although Elav-like Hu proteins alterations were reported in diabetes or neuropathy, little is known about the regulation of neuron-specific Elav-like Hu RNA-binding proteins in sensory neurons of dorsal root ganglia (DRG) due to the diabetic condition. The goal of our study was to analyze the gene and protein expression of HuB, HuC, and HuD in DRG sensory neurons in diabetes. The diabetic condition was induced in CD-1 adult male mice with single-intraperitoneal injection of streptozotocin (STZ, 150 mg/kg), and 8-weeks (advanced diabetes) after induction was quantified the Elav-like proteins expression. Based on the glycemia values, we identified two types of responses to STZ, and mice were classified in STZ-resistant (diabetic resistant, glycemia < 260 mg/dL) and STZ-sensitive (diabetic, glycemia > 260 mg/dL). Body weight measurements indicated that 8-weeks after STZ-induction of diabetes, control mice have a higher increase in body weight compared to the diabetic and diabetic resistant mice. Moreover, after 8-weeks, diabetic mice (19.52 ± 3.52 s) have longer paw withdrawal latencies in the hot-plate test than diabetic resistant (11.36 ± 1.92 s) and control (11.03 ± 1.97 s) mice, that correlates with the installation of warm hypoalgesia due to the diabetic condition. Further on, we evidenced the decrease of Elav-like gene expression in DRG neurons of diabetic mice (Elavl2, 0.68 ± 0.05 fold; Elavl3, 0.65 ± 0.01 fold; Elavl4, 0.53 ± 0.07 fold) and diabetic resistant mice (Ealvl2, 0.56 ± 0.07 fold; Elavl3, 0.32 ± 0.09 fold) compared to control mice. Interestingly, Elav-like genes have a more accentuated downregulation in diabetic resistant than in diabetic mice, although hypoalgesia was evidenced only in diabetic mice. The Elav-like gene expression changes do not always correlate with the Hu protein expression changes. To detail, HuB is upregulated and HuD is downregulated in diabetic mice, while HuB, HuC, and HuD are downregulated in diabetic resistant mice compared to control mice. To resume, we demonstrated HuD downregulation and HuB upregulation in DRG sensory neurons induced by diabetes, which might be correlated with altered post-transcriptional control of RNAs involved in the regulation of thermal hypoalgesia condition caused by the advanced diabetic neuropathy.

Advances in the study of RNA-binding proteins in diabetic complications

“…They found that HuR can bind to MMP-9, thus enhancing its stability, which promotes wound healing [ 171 ]. In diabetic neuropathy, a study demonstrated that, in diabetes, HuD downregulation and HuB upregulation occurred in dorsal root ganglia sensory neurons, which may be associated with mRNA involved in DRG neuronal excitability [ 173 ].…”

Spatial characterization of tangle-bearing neurons and ghost tangles in the human inferior temporal gyrus with three-dimensional imaging

“… 2 , 14 - 16 HuD E-1 antibody binds to the ELAV like RNA-binding protein 1, which localizes to the nucleoplasm, nucleoli and cytosol of neurons. 17 , 18 DAPI is a small molecule that binds strongly to adenine–thymine rich regions of double-stranded DNA and localizes to the nucleus of any DNA-containing cell. 19 …”

Ameliorative Effect of <i>Moringa Oleifera</i> Biochemical Constituents on Blood Glucose Level of Streptozocin-Induced Diabetic Wistar Rats

“…This result agree with finding reported by Mostafavinia et al, 2016 [14] whose reported STZ to be considered as one of the most used diabetogenic compound for inducing diabetes in experimental animal models. Many reports indicated that STZ is capable of producing mild to severe types of diabetes that vary according to the selected dose, strain, and age of animals, nutritional status, and route of administration, along with other factors [15]. Moringa oleifera have been shown to have glucose lowering effect in hyperglycemic streptozocin induced diabetic rats.…”