WD9-1
Effects of diosgenin on motor function and axonal repairing in spinal cord injured mice
脊髄損傷マウスの運動機能回復と軸索修復へのジオスゲニンの作用
Nakano Aoi（中野 葵），東田 千尋
Div. of Neuromedical Sci, Inst. of Natural Med, Univ. of Toyama
Motor dysfunction in spinal cord injury (SCI) is caused by disruption of axons in the spinal cord. Although several treatable options have been proposed in experimental levels, practical applications are hardly established. For SCI therapy, potent axonal repairing is required.We have focused on diosgenin as a prominent compound that extends and repairs axons. We previously accumulated evidences of memory improvement by diosgenin and its signaling mechanism leading to axonal repairing. However, effects of diosgenin on SCI had not been investigated. Therefore, we aimed to clarify therapeutic effects of diosgenin on the motor function and axonal restoration in SCI mice to evaluate that diosgenin could be promising therapeutic drug for SCI.Diosgenin was administered for 14 days to contusive SCI mice (ddY, female, 8-week old) by i.p. injection at a dose of 10 μmol/kg. Motor function was evaluated by the Basso Mouse Scale for Locomotion (BMS) and Body support score (BSS, *established by us, Teshigawara et al.,2013). Diosgenin significantly improved those scores. However, the degree of recovery was partial. Our study indicated that effects of diosgenin depended on distribution to the target tissue (Tohda et al., 2017). Therefore, we tried to more direct administration of diosgenin to the lesion site. Chronic intrathecal injection of diosgenin using a detained catheter was applied for 13 days to complete transection at T10 level. Vehicle solution-injected mice showed very severe dysfunction of hindlimbs. In contrast, motor recovery was observed in a part of diosgenin-injected mice. Axonal growth in the spinal cord of those mice is now evaluated. In conclusion, diosgenin has potential to recover motor function in SCI. | | WD9-2
Neuropilin-1-mediated pruning of corticospinal tract fiber contributes to motor recovery after spinal cord injury
Neuropilin-1による皮質脊髄路の軸索側枝の刈り込みは脊髄損傷後の運動機能回復に寄与する
Nakanishi Toru（中西 徹）1,2，藤田 幸1,3，山下 俊英1,3,4
1Dept of Mol Neurosci, Grad Sch of Med, Osaka Univ
2JSPS Research Fellow
3IFReC, Osaka Univ
4Grad Sch of Frontier Biosci, Osaka Univ
While complete spinal cord injury (SCI) often leads to the permanent motor, sensory and autonomic disorders, some recovery including motor function can be followed after incomplete SCI. Recent studies suggested that this motor recovery was attributed to the reorganization of corticospinal tract (CST), which is the main motor pathway and regulates the voluntary movement. In the course of the reorganization, axotomized CST fibers form collaterals and make synapses with propriospinal neurons, and then the excess collaterals are pruned. Although the pruning is considered to elaborate the neural pathway, its molecular mechanism and functional role remain poorly understood. To address these issues, we employed incomplete SCI model mice undergoing dorsal hemisection at thoracic level 8. By in situ hybridization, we found that Neuropilin-1 (Nrp1) mRNA was upregulated in layer 5 pyramidal neurons especially in the motor cortex 14 days after SCI, when the pruning occurred. Using adeno associated virus (AAV) vector encoding Nrp1 shRNA, we demonstrated that Nrp1 knockdown in the hindlimb motor area suppressed not the sprouting but the pruning of collaterals after SCI. Retrograde labeling and immunohistochemistry revealed that propriospinal neurons expressed Semaphorin 3A, which is the ligand for Nrp1. We further showed that the genetic deletion of Nrp1 specifically in the hindlimb motor area impaired the recovery of skilled movement at 21 and 28 days after SCI. Together our results suggest that the pruning of collaterals mediated by Nrp1 is required for the motor recovery after SCI. |
