The complications of diabetic polyneuropathy (DN) determines its level of severity. It may occur with distinctive clinical symptoms (painful DN) or appears undetected (painless DN). This study aimed to investigate microglia activation and signalling molecules brain-derived neurotrophic factor (BDNF) and downstream regulatory element antagonist modulator (DREAM) proteins in spinal cord of streptozotocin-induced diabetic neuropathy rats. Thirty male Sprague-Dawley rats (200-230 g) were randomly assigned into three groups: (1) control, (2) painful DN and (3) painless DN. The rats were induced with diabetes by single intraperitoneal injection of streptozotocin (60 mg/kg) whilst control rats received citrate buffer as a vehicle. Four weeks post-diabetic induction, the rats were induced with chronic inflammatory pain by intraplantar injection of 5% formalin and pain behaviour responses were recorded and assessed. Three days later, the rats were sacrificed and lumbar enlargement region of spinal cord was collected. The tissue was immunoreacted against OX-42 (microglia), BDNF and DREAM proteins, which was also quantified by western blotting. The results demonstrated that painful DN rats exhibited increased pain behaviour score peripherally and centrally with marked increase of spinal activated microglia, BDNF and DREAM proteins expressions compared to control group. In contrast, painless DN group demonstrated a significant reduction of pain behaviour score peripherally and centrally with significant reduction of spinal activated microglia, BDNF and DREAM proteins expressions. In conclusions, the spinal microglia activation, BDNF and DREAM proteins correlate with the pain behaviour responses between the variants of DN.
Neurotrophin is a growth factor that regulates the development and repair of the nervous system. From all factors, two pioneer groups, the nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF), have been widely explored for their role in disease pathogenesis and potential use as therapeutic agents. Nonetheless, neurotrophin-3 (NT3) and neurotrophin-4 (NT4) also have promising potential, albeit less popular than their counterparts. This review focuses on the latter two factors and their roles in the pathogenesis of brain disorders and potential therapies. An extensive literature search of NT3 and NT4 with their receptors, the TrkB and TrkC on the nervous system were extracted and analyzed. We found that NT3 and NT4 are not only involved in the pathogenesis of some neurodegenerative diseases, but also have promising therapeutic potential on injury- and vascular-related nervous system disease, neuropsychiatry, neurodegeneration and peripheral nerve diseases. In conclusion, the role of NT3 and NT4 should be further emphasized, and more studies could be explored on the potential use of these neurotrophins in the human study.