Fig. 6: LRRK2 inhibition alleviates CCI-induced brain lesions and neuronal loss.
a Experiment scheme for drug application, behavioral tests, and brain preparation. b, c Levels of total and phospho-S935 LRRK2 in brain lysates from each experiment group. β-actin antibodies were used as a loading control. Representative immunoblots (c) and quantification of total and phospho-LRRK2 levels relative to vehicle-injected sham group are presented. Bar graph in C shows means ± s.d. (n = 4–5). d Representative whole brain images of sham and CCI group. e Nissl staining of coronal brain sections from sham and CCI group. Scale bar = 2 mm. f Quantification of lesion volume, which is presented as percentage of total ipsilateral hemisphere. Bar graph shows means ± s.d. (n = 4–5). g Coronal brain sections from sham and CCI group treated with G1023 or vehicle control immunostained with NeuN antibodies. Magnified images of cortical and hippocampal regions are presented in right. Scale bar = 2 mm (whole brain sections) and 50 μm (magnified images). h Numbers of NeuN-positive cells (per mm2) in brain sections from sham and CCI groups treated with G1023 or vehicle control. Bar graphs show means ± s.d. (n = 4–5). i, j TUNEL assay. Representative image (i) and numbers (j) of TUNEL-positive cells (per mm2) in sham and CCI groups treated with G1023 or vehicle control are presented. Bar graph in (j) shows means ± s.d. (n = 4–5). Scale bar in i = 50 μm. k Immunoblots of sham and CCI groups treated with G1023 or vehicle control, using antibodies against Bcl-2, cleaved caspase-3, total and cleaved PARP, and p53. β-actin antibodies were used as a loading control. One-way ANOVA followed by Newman–Keuls post hoc test was performed for (c), (h), and (j) and Student t test was performed for (f). ***p < 0.001
