The Journal of Neuroscience, November 23, 2005, ():
Choroid Plexus Megalin Is Involved in Neuroprotection by Serum Insulin-Like Growth Factor I
J. Neurosci. Carro et al.
25: 10884
Supplemental data
Files in this Data Supplement:
- supplemental material
-
Supplemental Figure 1: Megalin is required for transport of Aβ carriers across choroid plexus epithelial cells. A, expression of siMeg in rat choroid plexus cultures abrogates IGF-I-induced passage of Aβ through the cell monolayer. B, siMeg also abolishes passage of albumin induced by IGF-I. C,D rat choroid plexus cells expressing miniMeg translocate significantly more Aβ (C) and albumin (D). E, expression of siMeg by choroid plexus cells also results in significantly decreased levels of TTR in the lower chamber of the culture well after IGF-I. F, IGF-I (100 nM, 24 hours) stimulates TTR production by choroid plexus cell monolayers. *p<0.05 and **p<0.01 vs HIV-infected cultures (n=of at least 3, in all experiments).
- supplemental material
-
Supplemental Figure 2: Megalin in animal models of cognitive deterioration. A, APP/PS1 mice show decreased water maze performance (acquisition and retention) that is improved by 6 months expression of miniMeg in choroid plexus. On the contrary, expression of siMeg in APP/PS1 mice deteriorated even further memory (retention) scores in the water maze without affecting already deteriorated learning (acquisition). Histograms: levels of Hpf-tau were inversely correlated to megalin activity in choroid plexus of APP/PS1 mice. siMeg increased Hpf-tau while miniMeg elicited the opposite effect. siMeg also resulted in increased Aβ1-40 in APP/PS1 mice (n=8 per group). B, in LID mice expression of miniMeg in the choroid plexus for 3 months significantly improved performance in the water maze: acquisition and retention scores were reduced. miniMeg also decreased brain Hpf-tau levels in LID mice as compared to HIV controls. C, Old rats were unable to learn the location of the hidden platform in the water-maze and 6 month expression of miniMeg in the choroid plexus did not improve their performance (n=6). *p<0.05; **p<0.01; and ***p<0.001 vs HIV-infected controls by one-way ANOVA followed by Studentīs t-test.
