Swimming Exercise Induced Reversed Expression of miR-96 and Its Target Gene NaV1.3 in Diabetic Peripheral Neuropathy in Rats

Abstract

Diabetes is a common metabolic disease which leads to diabetic peripheral neuropathy. Recently, the role of microRNA-96 (miR-96) in alleviating neuropathic pain by inhibiting the expression of NaV1.3, an isoform of voltage-gated sodium channels, has been shown. Peripheral nerve injuries result in NaV1.3 elevation. Exercise has beneficial role in diabetes management and peripheral neuropathy. However, the effects of exercise on miR-96 and its target gene NaV1.3 in diabetic rats are unknown. Therefore, the present study investigated the effects of exercise training on the expression of miR-96 and NaV1.3 in diabetic rats. For this purpose, rats were randomly divided into four groups: control, exercise, diabetic and diabetic-exercise groups. Type 2 diabetes was induced by a high-fat diet and the administration of streptozotocin (STZ) (35 mg/kg, i.p.). The exercise groups were subjected to swimming exercise 5 days/week for 10 weeks. At the end of the treatment period, thermal pain threshold, determined through the tail-flick test, and the expression levels of miR-96 and its target gene NaV1.3 were determined by reverse transcription (RT)-PCR in the sciatic nerve tissues of the rats. Data of the present study indicated that diabetes diminished miR-96 expression levels, but significantly upregulated NaV1.3 expression in the sciatic nerve. On exercise training, miR-96 expression was reversed with concurrent down-regulation of the NaV1.3 expression. This study introduced a new and potential miRNA-dependent mechanism for exerciseinduced protective effects against diabetic thermal hyperalgesia.

miR‐96‐5p regulates wound healing by targeting BNIP3/FAK pathway

“…16,17 Additionally, miR-96-5p modulates cell proliferation, invasion, and migration in different diseases. 18,19 However, the role of miR-96-5p in wound healing has not been illustrated. Our study indicated that miR-96-5p was significantly decreased during the wound healing process, which is opposite to BNIP3 expression.…”

“…miR‐96‐5p was reported to promote gastric, prostate, and cervical cancers . Additionally, miR‐96‐5p modulates cell proliferation, invasion, and migration in different diseases . However, the role of miR‐96‐5p in wound healing has not been illustrated.…”

Exercise and Neuropathic Pain: A General Overview of Preclinical and Clinical Research

“…Further, there is consistent evidence that 7-14 weeks of treadmill running reduced mechanical indices of nociception in SCI models of neuropathic pain [38,39,45]. While there is less literature in DPN, CIPN, and CRPS models, in general, 4-10 weeks of treadmill running [48,49,51,52,54], 4-10 weeks of swim training [47,50,53], and 23-28 days of wheel running [55] ameliorated abnormal nociception in these models. Other durations of exercise training are less conclusive [17,24,25,[40][41][42]44], suggesting there may be an optimal exercise duration for effective neuropathic pain management.…”

Mechanisms of exercise for diabetic neuropathic pain

“…Chen et al (2014) showed that enhanced NaV1.3 expression exacerbated neuropathic pain, and that among microRNAs, miR-96 alleviated neuropathic pain by decreasing the expression of NaV1.3. Aghdam et al (2018) established a DNP rat model by intraperitoneal injection of STZ and with a high-fat diet for 1 month to elucidate the effect of exercise on miR-96 and NaV1.3. Rats were subjected to 10 weeks of swimming exercise, after which real-time quantitative PCR was conducted to measure the expression of miR-96 and NaV1.3.…”