Journal: Frontiers in Cellular Neuroscience

Article Title: Oral Treatments With the TrkB Ligand Prodrug, R13, Promote Enhanced Axon Regeneration Following Peripheral Nerve Injury

doi: 10.3389/fncel.2022.857664

Figure Lengend Snippet: Oral R13 treatment stimulates TrkB phosphorylation and a downstream effector at the site of nerve injury. On the left side of each panel, examples of blots of sciatic nerves at the site of injury prior to (0 min) and at 15, 30, 60, 120, 240, and 480 min after oral administration of R13 are shown. On the right are quantitative results from blots from four nerves ( n = 4). Bands of specific protein were densitometrically analyzed and normalized to the signal intensity of beta-actin. For each of the three proteins studied, the ratio of the expression of their activated (phosphorylated) form relative to total protein expression was calculated. Significance of differences at different times after administration from that prior to R13 administration was evaluated using an unpaired t -test: * p < 0.05 ** p < 0.01, n = 4. (A) Immunoblots for anti- phosphorylated TrkB (pTrkB Y705), TrkB, and beta-actin. (B) Immunoblots for anti- phosphorylated AKT (pAKT), AKT, and beta-actin. (C) Immunoblots for anti- phosphorylated MAP kinase (pMAPK/Erk1/2), MAPK/Erk1/2, and beta-actin.

Article Snippet: R13 was obtained from Sundia MediTech, Shanghai, China (Lot No: A0257-10014-16).

Techniques: Phospho-proteomics, Expressing, Western Blot

Journal: Frontiers in Cellular Neuroscience

Article Title: Oral Treatments With the TrkB Ligand Prodrug, R13, Promote Enhanced Axon Regeneration Following Peripheral Nerve Injury

doi: 10.3389/fncel.2022.857664

Figure Lengend Snippet: Oral R13 treatments enhance the number of motoneurons whose axons regenerated successfully. A. Image of a longitudinal section through lamina IX of the lumbar spinal cord of a mouse 4 weeks after sciatic nerve transection and repair and treatment with R13. Red and green fluorophores mark motoneurons retrogradely labeled from tracers injected into the reinnervated gastrocnemius (GAST) and tibialis anterior (TA) muscles, respectively. (A) Small number of motoneurons contain both labels (Both, yellow arrows). (B) Mean (± SEM, n = 8) numbers of labeled neurons in these three categories in vehicle-treated (V) and R13-treated mice. ** = p < 0.01, **** = p < 0.0001.

Article Snippet: R13 was obtained from Sundia MediTech, Shanghai, China (Lot No: A0257-10014-16).

Techniques: Labeling, Injection, Muscles

Journal: Frontiers in Cellular Neuroscience

Article Title: Oral Treatments With the TrkB Ligand Prodrug, R13, Promote Enhanced Axon Regeneration Following Peripheral Nerve Injury

doi: 10.3389/fncel.2022.857664

Figure Lengend Snippet: Oral R13 treatments promote regeneration of muscle afferent neurons. (A) Histological section through an L4 dorsal root ganglion (DRG) from a mouse treated with R13. Cell bodies of primary afferent neurons successfully reinnervating the gastrocnemius (GAST, red) or tibialis anterior (TA, green) muscles 4 weeks after sciatic nerve transection and repair are shown. Sensory neurons labeled by both tracers (yellow) are indicated by the yellow arrows. (B) Counts of labeled neurons (mean ± SEM, n = 6) in the L4 dorsal root ganglia of vehicle-treated and R13-treated mice. (C) Mean proportions of labeled DRG neurons in different size classes in the two different treatment groups. No significant differences were found between R13-treated and vehicle-treated mice. * = p < 0.05, **** = p < 0.0001.

Article Snippet: R13 was obtained from Sundia MediTech, Shanghai, China (Lot No: A0257-10014-16).

Techniques: Muscles, Labeling

Journal: Frontiers in Cellular Neuroscience

Article Title: Oral Treatments With the TrkB Ligand Prodrug, R13, Promote Enhanced Axon Regeneration Following Peripheral Nerve Injury

doi: 10.3389/fncel.2022.857664

Figure Lengend Snippet: (A) Direct muscle (M) responses recorded from gastrocnemius muscles in response to sciatic nerve stimulation are shown 4 weeks after sciatic nerve transection and repair from a mouse treated with oral R13 (upper trace), from a mouse treated with vehicle (middle trace), and from a mouse treated with oral 7,8-DHF (lower trace). (B) Mean (± SEM) scaled full wave rectified M response amplitudes recorded from gastrocnemius (GAST) and tibialis anterior (TA) muscles 4 weeks after sciatic nerve transection and repair and oral treatment with vehicle ( n = 8), 7,8-DHF ( n = 7), or R13 ( n = 7). The dashed horizontal line at unity represents the mean Mmax amplitude recorded from untreated mice 4 weeks after transection and repair of the sciatic nerve . ** p < 0.01, *** p < 0.001.

Article Snippet: R13 was obtained from Sundia MediTech, Shanghai, China (Lot No: A0257-10014-16).

Techniques: Muscles