Fig. 5

VCP-dependent Tau clearance via autophagy pathway is conserved in mice. a Experimental scheme of AAV-pSyn1-TauP301L, AAV-pSyn1-VCP, and chloroquine (CQ) delivery into the hippocampus of WT mice (9-month-old). b LC3 and pTau (S202/T205) by AT8 immunostaining was performed in the hippocampus of each mouse group injected with AAV- pSyn1-Control, AAV-pSyn1-TauP301L, AAV-pSyn1-TauP301L + AAV-pSyn1-VCP and AAV-pSyn1-TauP301L + AAV-pSyn1-VCP + CQ, respectively. The nuclei were counterstained with DAPI. White dotted lines indicate the shape of neurons. Scale bars (white) = 10 ?m. c LC3 and pTau intensity was significantly increased in TauP301L group compared to the Control group. VCP overexpression significantly decreased pTau level in TauP301L + VCP group compared to TauP301L group. CQ injection significantly increased the levels of LC3 and pTau. d An experimental flow of passive avoidance behavior test in mice after the injection with AAV-pSyn1-Control, AAV-pSyn1-TauP301L, AAV-pSyn1-TauP301L + AAV-pSyn1-VCP, and AAV-pSyn1-TauP301L + AAV-pSyn1-VCP + CQ. e Latency to dark room was significantly rescued in TauP301L + VCP group compared to TauP301L group. Whereas TauP301L + VCP + CQ-injected group showed a significant decrease of the time of latency to dark room compared to TauP301L + VCP group. Significance at *p < 0.05, **p < 0.01, ***p < 0.005 by Student?s t test. Data are presented as mean ± SEM. n = 4 (10 individual animals)