In the present study, we examined the effects of glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), and insulin growth factor (IGF-1) on adult motoneuron survival following spinal root avulsion. The expression of neuronal nitric oxide synthase (nNOS), c-Jun, and the low-affinity neurotrophin receptor (P75) following treatment with these neurotrophic factors was also examined. In control animals, approximately 80% of spinal motoneurons were nNOS positive at 3 weeks following the lesion, whereas in GDNF or BDNF treated animals no nNOS positive motoneurons were found at the same time point. Following injury and treatment with GDNF and BDNF increased numbers of motoneurons were c-Jun and P75 positive. By 6 weeks following the lesion, only approximately 28% of motoneurons persisted in control animals whereas about 90% of motoneurons survived injury following treatment with either GDNF or BDNF. In contrast, CNTF and IGF-1 were ineffective in either inhibiting nNOS expression or preventing motoneuron death. Our results provide in vivo evidence that the survival of injured adult mammalian motoneurons can be promoted by specific neurotrophic factors, and that this effect is associated with inhibition of nNOS expression and up-regulation of c-Jun and P75 expression.

Peripheral nerves are fragile and easily damaged, usually resulting in nervous tissue loss, motor and sensory function loss. Advances in neuroscience and engineering have been significantly contributing to bridge the damage nerve and create permissive environment for axonal regrowth across lesions. We have successfully designed two self-assembling peptides by modifying RADA 16-I with two functional motifs IKVAV and RGD. Nanofiber hydrogel formed when combing the two neutral solutions together, defined as RADA 16-Mix that overcomes the main drawback of RADA16-I associated with low pH. In the present study, we transplanted the RADA 16-Mix hydrogel into the transected rat sciatic nerve gap and effect on axonal regeneration was examined and compared with the traditional RADA16-I hydrogel. The regenerated nerves were found to grow along the walls of the large cavities formed in the graft of RADA16-I hydrogel, while the nerves grew into the RADA 16-Mix hydrogel toward distal position. RADA 16-Mix hydrogel induced more axons regeneration and Schwann cells immigration than RADA16-I hydrogel, resulting in better functional recovery as determined by the gait-stance duration percentage and the formation of new neuromuscular junction structures. Therefore, our results indicated that the functional SAP RADA16-Mix nanofibrous hydrogel provided a better environment for peripheral nerve regeneration than RADA16-I hydrogel and could be potentially used in peripheral nerve injury repair.

Controlled delivery of myofibril components to the appropriate sites of assembly is crucial for myofibrillogenesis. Here, we show that kinesin-1 heavy chain Kif5b plays important roles in anterograde transport of α-sarcomeric actin, non-muscle myosin IIB, together with intermediate filament proteins desmin and nestin to the growing tips of the elongating myotubes. Mice with Kif5b conditionally knocked out in myogenic cells showed aggregation of actin filaments and intermediate filament proteins in the differentiating skeletal muscle cells, which further affected myofibril assembly and their linkage to the myotendinous junctions. The expression of Kif5b in mutant myotubes rescued the localization of the affected proteins. Functional mapping of Kif5b revealed a 64-amino acid α-helix domain in the tail region, which directly interacted with desmin and might be responsible for the transportation of these proteins in a complex.

This study was undertaken to elucidate the molecular mechanisms by which lithium regulates the development of spinal cord‐derived neural progenitor cells (NPCs)in vitroand after transplantedin vivo. Our results show that lithium at the therapeutic concentration significantly increases the proliferation and neuronal differentiation of NPCsin vitro.Specific ELISAs, western blotting, and quantitative real‐time RT‐PCR assays demonstrate that lithium treatment significantly elevates the expression and production of brain‐derived neurotrophic factor (BDNF) by NPCs in culture. Application of a BDNF neutralizing antibody in culture leads to a marked reduction in the neurogenesis of lithium‐treated NPCs to the control level. However, it shows no effects on the proliferation of lithium‐treated NPCs. These findings suggest that the BDNF pathway is possibly involved in the supportive role of lithium in inducing NPC neurogenesis but not proliferation. This study also provides evidence that lithium is able to elevate the neuronal generation and BDNF production of NPCs after transplantation into the adult rat ventral horn with motoneuron degeneration because of spinal root avulsion, which highlights the therapeutic potential of lithium in cell replacement strategies for spinal cord injury because of its ability to promote neuronal differentiation and BDNF production of grafted NPCs in the injured spinal cord.