TrkB expression.

<p>(<b>A</b>) Two forms of trkB are noted: full length form (140 kDa) and truncated form (90∼95 kDa). Ischemia decreased the full-length protein in the ipsilateral region (Ipsi). Exercise increased two forms of the protein in both hemispheres, particularly contralateral (Contra) to the ischemic hemisphere (p<0.05, n = 7). (<b>B</b>) Expression of two forms of protein increased at day 23 after ischemia. Exercise increased the full-length form in both hemispheres at day 16 and increased the truncated form by day 16, particularly in the contralateral hemisphere (p<0.05, n = 6). (<b>C</b>) (a) Immunoreactivities in the ischemic region. (b) Exercise increased the immunoreactivities adjacent to the ischemic region in the ipsilateral hemisphere. (c) In the control hemisphere, exercise increased immunoreactivities, particularly in vascular structures. ▄ = 100 um.</p

Experimental design.

<p>Among total of 59 rats, 35 rats underwent middle cerebral artery occlusion (MCAO), and 12 rats were used as sham-operated control. In 48 hours, the MCAO group was divided into either the exercise (n = 18) or non-exercise group (n = 17). Twelve rats were additionally used for determination of temporal change in the ischemic-exercise group (n = 12, n = 4 each and sacrificed at 9, 16, and 23 days following ischemia).</p

Amelioration of Huntington's disease phenotypes by Beta-Lapachone is associated with increases in Sirt1 expression, CREB phosphorylation and PGC-1α deacetylation

<div><p>Huntington’s disease (HD) is one of the most devastating genetic neurodegenerative disorders with no effective medical therapy. β-Lapachone (βL) is a natural compound obtained from the bark of the Lapacho tree and has been reported to have beneficial effects on various diseases. Sirt1 is a deacetylase of the sirtuin family and deacetylates proteins including the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) which is associated with mitochondrial respiration and biogenesis. To examine the effectiveness of βL on HD, βL was orally applied to R6/2 HD mice and behavioral phenotypes associated with HD, such as impairment of rota-rod performance and increase of clasping behavior, as well as changes of Sirt1 expression, CREB phosphorylation and PGC-1α deacetylation were examined. Western blot results showed that Sirt1 and p-CREB levels were significantly increased in the brains of βL-treated R6/2 mice. An increase in deacetylation of PGC-1α, which is thought to increase its activity, was observed by oral administration of βL. In an <i>in vitro</i> HD model, βL treatment resulted in an attenuation of MitoSOX red fluorescence intensity, indicating an amelioration of mitochondrial reactive oxygen species by βL. Furthermore, improvements in the rota-rod performance and clasping score were observed in R6/2 HD mice after oral administration of βL compared to that of vehicle control-treated mice. Taken together, our data show that βL is a potential therapeutic candidate for the treatment of HD-associated phenotypes, and increases in Sirt1 level, CREB phosphorylation and PGC-103B1 deacetylation can be the possible underlying mechanism of the effects of βL.</p></div

Reduction in PGC-1α acetylation by βL administration in mice.

<p>βL was orally administered to R6/2 mice for 6 weeks from 5 to 11 weeks of age. After the sacrifice, brains were isolated and an immunoprecipitation was performed using the PGC-1α antibody. Immunoprecipitated proteins were separated by SDS-PAGE and blotted with anti-PGC-1α and anti-acetylated-lysine antibodies to measure the level of PGC-1α acetylation. Relative band intensities were analyzed using the Image J software. The acetylation level of PGC-1α was analyzed by the intensity of acetylated lysine relative to the amount of total PGC-1α (lower panel). The graph shows means ± SEM. *p < 0.01 indicates significant differences when compared to the control group.</p

Decrease in mitochondrial superoxide level by βL treatment of an <i>in vitro</i> HD model.

<p>R6/2 mouse-derived NSCs were cultured and differentiated in a differentiation medium. After differentiation, βL was added for 3 days and mitochondrial superoxide levels were measured by immunocytochemistry (A) and flow cytometry (B) after MitoSOX red staining. The red, roundish objects are individual cells with MitoSOX staining, and the M1 marker of the flow cytometry result indicats a Cy3-positive population. The percentage values of NSCs with M1 after vehicle or βL treatment are represented in a bar graph (n = 3) (C). The graph shows means ± SEM. *p < 0.05 indicates significant differences when compared to the vehicle-treated group.</p

MOESM1 of SP, CGRP changes in pyridoxine induced neuropathic dogs with nerve growth factor gene therapy

Additional file 1: Figure S1. Nerve growth factor (NGF) immunostaining of the dorsal root ganglion (DRG) in the vehicle-treated (A), and NGF gene-treated (B) groups at 4 weeks after 1 week of pyridoxine injection. In the vehicle-treated group, NGF immunoreactive neurons are not detectable in the DRG. In the NGF gene-treated group, NGF immunoreactive neurons are abundantly observed in the DRG. Scale bar = 50 μm